Use of enzyme-modified isoquercitrin

ABSTRACT

The present invention provides a salivator that is in a form for use in the mouth (a form for intraoral use), or in a form for use by oral administration (a form for oral administration). The salivator can be prepared by using enzymatically modified isoquercitrin, or a combination of enzyme-modified isoquercitrin and a thickening polysaccharide. The present invention further provides an additive that is useful for preparing an oral composition (a food or beverage, a pharmaceutical product for oral administration)(an additive for an oral composition) and that can impart at least one effect selected from the group consisting of a salivation-promoting effect, a deglutition-improving effect (swallowing-assisting effect), and a mastication-improving effect (chewing-assisting effect) to the oral composition. The additive can be prepared by using a combination of enzymatically modified isoquercitrin and a thickening polysaccharide.

TECHNICAL FIELD

The present invention relates to the use of enzymatically modifiedisoquercitrin. More specifically, the present invention relates to theuse of enzymatically modified isoquercitrin as a salivator, inparticular, as a salivator in a form for use in the mouth (a form forintraoral use), or in a form for use by oral administration (a form fororal administration).

The present invention further relates to the use of enzymaticallymodified isoquercitrin as an additive for compositions for intraoral useor oral intake, such as foods and beverages or pharmaceutical products,so as to impart to the compositions at least one effect selected fromthe group consisting of a salivation-promoting effect, adeglutition-improving effect (swallowing-assisting effect) and amastication-improving effect (chewing-assisting effect).

BACKGROUND ART

Saliva plays an important role, for example, in mouth functions andmaintenance of the intraoral environment. Examples of mouth functionsinclude the function of smoothening utterance and conversation, foodintake function, and swallowing function. In particular, with respect tothe food or beverage intake function and swallowing function, saliva isdeeply involved in the action of forming an alimentary bolus, digestiveactivity by amylase secretion, and the action of maintaining tastesensation by solubilizing tastants and secreting carbonatedehydrogenase. Further, for maintenance of the intraoral environment,saliva is deeply involved in the self-cleaning effect in the mouthincluding the teeth, teeth remineralization effect, antibacterialeffect, immunization effect, anti-inflammatory effect, andtissue-repair-promoting effect by growth factors etc.

However, the amount of saliva secretion is known to be reduced byvarious diseases, such as emotional and stress disorders, neurosis,organ dysfunction, encephalitis, tumors, cerebrovascular disorder,hypertension, Basedow's disease, and diabetes; side effects of medicine;radiation therapy; aging; etc. In particular, in the elderly, not onlysalivary gland function reduction by aging but also multiple chronicdiseases and therapeutic agents for such diseases reduce the amount ofsaliva secretion; therefore, many people currently complain of drymouth.

The reduction of salivary secretion makes the mouth dry, which leads todifficulty in chewing and swallowing, and lowers digestive function. Drymouth also causes an unpleasant sensation in the mouth, and halitosis.Further progression of such symptoms causes periodontal diseases andinfectious diseases in the mouth, such as stomatitis. Therefore, thereis a need to increase the amount of salivary secretion by some kind ofmeans.

As means for increasing the amount of saliva secretion, a gustatorystimulation method using acidulation (Patent Literature (PTL) 1) and anolfactory stimulation method (PTL 2) have been proposed. Methods using aplant extract having a salivation-promoting effect or a component of theplant extract (PTL 3 to PTL 8), a method using a pharmaceuticalsubstance targeting a muscarinic receptor (PTL 9), and a method using apharmaceutical substance targeting PAR-2 (PTL 10) have also beenproposed.

However, some of the methods disclosed in the above documents areinsufficient in terms of strength and sustainability of the effect, andalso have the following problems.

The method disclosed in PTL 1 finds only limited use in view ofpalatability. Furthermore, because of strong stimulation, frequent useof this method may affect oral tissues, such as dissolution of theteeth, stimulation of oral mucosa, etc. The method disclosed in PTL 2has a problem such that the effect is lost with the disappearance ofolfactory stimuli. The methods disclosed in PTL 3 to PTL 6 have aproblem such that the methods can be applied to only limited types ofcompositions (food compositions, and compositions for intraoral use)because many of the plant extracts used in these methods have a specificstimulus, taste, and flavor, and using such extracts with an organicacid is essential or recommended. Further, the methods disclosed in PTL9 and PTL 10 use pharmaceutical substances; therefore, the use of suchmethods may be limited.

Quercetin, a kind of flavonoid, has recently been reported to have asalivation-enhancing effect (Non-patent Literature (NPL) 1). Morespecifically, it has been reported that administering quercetin to modelmice having disturbance of salivary secretion created by radiationexposure reduces hyposalivation, and that administering quercetin tonormal mice enhances saliva secretion. With respect to the actionmechanism of quercetin in the saliva secretion, NPL 1 discloses thatsaliva secretion is promoted by enhancing the expression of aquaporin 5and uptake of ions into cells. However, these are all data of quercetinintake by mice. NPL1 nowhere mentions a case of quercetin intake byhumans.

CITATION LIST Patent Literature

-   PTL 1: JPH7-101856A-   PTL 2: JP2003-40752A-   PTL 3: JPH11-71253A-   PTL 4: JPH10-182392A-   PTL 5: JP2002-265375A-   PTL 6: JP2005-162633A-   PTL 7: WO2009/060915-   PTL 8: JP2009-531287A-   PTL 9: JPH8-12575A-   PTL 10: JP2001-64203A

Non-Patent Literature (NPL)

-   Non-patent Literature (NPL) 1: Ichiro Saito et al., PLOS ONE, DOI,    10.1371/journal.pone.0116008 Jan. 28, 2015

SUMMARY OF INVENTION Technical Problem

An object of the present invention is to provide a salivator, preferablya salivator that is used in the mouth of a human, or used by oraladministration to a human; and that promptly promotes saliva secretionafter intraoral application or oral administration (intake) of thesalivator, and can heal the dry mouth.

Further, another object of the present invention is to provide anadditive that is effective in preparing a composition for intraoral useor oral intake (a food or beverage, a pharmaceutical product) that iscapable of promoting saliva secretion (an additive for a composition forintraoral use or oral intake); and preferably an additive effective inpreparing a composition for intraoral use or oral intake that is capableof promoting saliva secretion in a person with reduced salivationfunction, and assisting chewing and swallowing. The additive ispreferably an additive suitable for compositions for intraoral use ororal intake that can impart the above effects to compositions forintraoral use or oral intake without giving undesirable simulation orflavor (taste, smell) to the mouth, or providing side effects that areharmful to human bodies. Another object of the present invention is toprovide a method for preparing the composition for intraoral use or oralintake by using the additive. A further object of the present inventionis to provide the composition for intraoral use or oral intakecomprising the additive.

Solution to Problem

The present inventors conducted extensive research to achieve the aboveobjects, and found that enzymatically modified isoquercitrin has asalivation-promoting effect. More specifically, as shown in ExperimentalExample 1 described below, the present inventors found that applicationof enzymatically modified isoquercitrin to the mouth of a human, or oralintake of enzymatically modified isoquercitrin promptly promotes salivasecretion and increases the amount of secretion. In contrast, whenα-glucosylrutin, which, like enzymatically modified isoquercitrin, is aquercetin glycoside having a quercetin structure, or quercetin itselfwas administered to a human in an equimolar amount relative to theenzymatically modified isoquercitrin, in terms of rutin, nosalivation-promoting effect (saliva secretion-increasing effect) wasconfirmed. These results confirm that, among the above-mentionedflavonoids, only enzymatically modified isoquercitrin can immediatelyexhibit a salivation-promoting effect (saliva secretion-increasingeffect) by application to the mouth of a human or oral administration toa human, and that this effect is specific to enzymatically modifiedisoquercitrin. Further, as shown in Experimental Example 2, thesalivation-promoting effect (saliva secretion-increasing effect) of theenzymatically modified isoquercitrin is significantly increased by usinga polysaccharide for thickening with the enzymatically modifiedisoquercitrin, or by thickening the test sample. Such enhancement of thesalivation-promoting effect (saliva secretion-increasing effect) byincorporating a thickening polysaccharide or by thickening is alsospecific to enzymatically modified isoquercitrin, and was not observedin α-glucosylrutin or quercetin itself.

The present inventors conducted further research based on this finding,and confirmed that, in particular, when a thickening polysaccharide isused in a proportion of 0.2 to 500 parts by mass per part by mass ofenzymatically modified isoquercitrin, the salivation-promoting effect ofthe enzymatically modified isoquercitrin can be enhanced withoutsignificantly affecting palatability (taste, smell, etc.) of the targetcomposition for intraoral use or oral intake (a food or beverage, acomposition).

The present inventors conducted further research based on thesefindings, and have accomplished the present invention. The presentinvention includes the following embodiments.

(A) Use as Salivator (A-I) Salivator

(A-I-1) A salivator comprising enzymatically modified isoquercitrin asan active ingredient.(A-I-2) The salivator according to (I-1), further comprising athickening polysaccharide.(A-I-3) The salivator according to (A-I-1) or (A-I-2), wherein thethickening polysaccharide is at least one member selected from the groupconsisting of xanthan gum, locust bean gum, guar gum, tara gum,deacylated gellan gum, highly acylated gellan gum, pectin, alginates,gelatin, agar, psyllium seed gum, and carrageenan.(A-I-4) The salivator according to any one of (A-I-1) to (A-I-3), whichis a composition for intraoral use or oral intake.(A-I-5) The salivator according to any one of (A-I-1) to (A-I-4), whichis a composition for intraoral use or oral intake, the composition beingfor a human with reduced salivation function (a person with reducedsalivation function), or a human with reduced swallowing function (aperson with reduced deglutition function).(A-I-6) The salivator according to any one of (A-I-1) to (A-I-5), whichis a composition for intraoral use or oral intake, the composition beingfor a healthy person whose mouth is in a dry state. The mouth in a drystate is not particularly limited. Examples include the mouth in a drystate on exercising, bathing, waking, etc.(A-I-7) The salivator according to any one of (A-I-1) to (A-I-6),wherein the salivator is in the form of a syrup, health drink, liquid,emulsion, oil, spray, gel, paste, tablet, chewable agent, lozenge, pill,granule, powder (powdered medicine), dry syrup, film, or stick-shapedpreparation.

The “salivator” of the present invention promotes salivation to therebyachieve the effect of increasing the amount of saliva secretion. In thismeaning, the embodiment of the present invention includes “salivasecretion (amount) increasing agents.”

(A-II) Method for Preparing Salivator

(A-II-1) A method for preparing a salivator, comprising incorporatingenzymatically modified isoquercitrin.(A-II-2) The method according to (A-II-1), comprising furtherincorporating a thickening polysaccharide.(A-II-3) The method according to (A-II-1) or (A-II-2), wherein thethickening polysaccharide is at least one member selected from the groupconsisting of xanthan gum, locust bean gum, guar gum, tara gum,deacylated gellan gum, highly acylated gellan gum, pectin, alginates,gelatin, agar, psyllium seed gum, and carrageenan.(A-II-4) The method according to any one of (A-II-1) to (A-II-3),further comprising processing the salivator into a form for intraoraluse or oral administration.(A-II-5) The method according to any one of (A-II-1) to (A-II-4),wherein the form for intraoral use or oral administration is a syrup,health drink, liquid, emulsion, oil, spray, gel, paste, tablet, chewableagent, lozenge, pill, granule, powder (powdered medicine), dry syrup,film, or stick-shaped preparation.

(A-III) Use for Producing Salivator

(A-III-1) Use of enzymatically modified isoquercitrin for producing asalivator.(A-III-2) Use of enzymatically modified isoquercitrin and a thickeningpolysaccharide for producing a salivator.(A-III-3) The use according to (A-III-2), wherein in the production of asalivator, the enzymatically modified isoquercitrin and the thickeningpolysaccharide are used separately, or in the form of a composition.(A-III-4) The use according to (A-III-2) or (A-III-3), wherein thethickening polysaccharide is at least one member selected from the groupconsisting of xanthan gum, locust bean gum, guar gum, tara gum,deacylated gellan gum, highly acylated gellan gum, pectin, alginates,gelatin, agar, psyllium seed gum, and carrageenan.(A-III-5) The use according to any one of (A-III-1) to (A-III-4),wherein the salivator is in a form for intraoral use or oraladministration.(A-III-6) The use according to any one of (A-III-1) to (A-III-5),wherein the form for intraoral use or oral administration is a form of asyrup, health drink, liquid, emulsion, oil, spray, gel, paste, tablet,chewable agent, lozenge, pill, granule, powdered medicine (powder), drysyrup, film, or stick-shaped preparation.

(A-IV) Method for Promoting Salivation

(A-IV-1) A method for promoting saliva secretion in a subject,comprising allowing the subject to orally ingest an effective amount ofthe salivator according to any one of (A-I-1) to (A-I-6).(A-IV-2) The method according to (A-IV-1), wherein the subject is ahuman with reduced saliva secretion function (a person with reducedsaliva secretion function) or a human with reduced swallowing function(a person with reduced deglutition function).(A-IV-3) The method according to (A-IV-1) or (A-IV-2), wherein thesubject is a human with hyposalivation or xerostomia.(A-IV-4) The method according to any one of (A-IV-1) to (A-IV-3),wherein the subject is a healthy person whose mouth is in a dry state.The mouth in a dry state is not particularly limited. Examples includethe mouth in a dry state on exercising, bathing, waking, etc.

The “method for promoting salivation” of the present invention alsoachieves the effect of increasing the amount of salivation by conductingthe method. In that meaning, this invention also includes “a method forincreasing saliva secretion (amount).”

(B) Use as an Additive for a Composition for Intraoral Use or OralIntake (I) Additive for a Composition for Intraoral Use or Oral Intake

(B-I-1) An additive for a composition for intraoral use or oral intakecomprising enzymatically modified isoquercitrin and a thickeningpolysaccharide.(B-I-2) The additive for a composition for intraoral use or oral intakeaccording to (B-I-1), wherein the thickening polysaccharide is at leastone member selected from the group consisting of xanthan gum, locustbean gum, guar gum, tara gum, deacylated gellan gum, highly acrylatedgellan gum, pectin, alginates, gelatin, agar, psyllium seed gum, andcarrageenan.(B-I-3) The additive for a composition for intraoral use or oral intakeaccording to (B-I-1) or (B-I-2), which contains the thickeningpolysaccharide in a proportion of 0.2 to 500 parts by mass per part bymass of the enzymatically modified isoquercitrin.(B-I-4) The additive for a composition for intraoral use or oral intakeaccording to (B-I-1) or (B-I-2), which is an additive for preparing asol composition for intraoral use or oral intake and contains thethickening polysaccharide in a proportion of 0.2 to 400 parts by mass,preferably 0.3 to 350 mass by parts, and more preferably 0.4 to 300parts by mass, per part by mass of the enzymatically modifiedisoquercitrin.(B-I-5) The additive for a composition for intraoral use or oral intakeaccording to (B-I-1) or (B-I-2), which is an additive for preparing agel composition for intraoral use or oral intake, and contains thethickening polysaccharide in a proportion of 1 to 500 parts by mass,preferably 2 to 450 parts by mass, and more preferably 2.5 to 350 partsby mass, per part by mass of the enzymatically modified isoquercitrin.(B-I-6) The additive for a composition for intraoral use or oral intakeaccording to (B-I-1) or (B-I-2), which is an additive for preparing aprocessed grain food or beverage, and contains the enzymaticallymodified isoquercitrin in a proportion of 0.01 to 3000 parts by mass,preferably 0.05 to 2000 parts by mass more, and more preferably 0.1 to1200 parts by mass, per part by mass of the enzymatically modifiedisoquercitrin.(B-I-7) The additive for a composition for intraoral use or oral intakeaccording to any one of (B-I-1) to (B-I-6), which is an additive in atleast one form selected from the group consisting of solids, pastes, andliquids.(B-I-8) The additive for a composition for intraoral use or oral intakeaccording to any one of (B-I-1) to (B-I-7), wherein the composition forintraoral use or oral intake is a food or beverage or a pharmaceuticalproduct.(B-I-9) The additive for a composition for intraoral use or oral intakeaccording to any one of (B-I-1) to (B-I-8), wherein the composition forintraoral use or oral intake is a food or beverage or a pharmaceuticalproduct that is ingested by or administered to at least one personselected from the group consisting of persons with reduced salivationfunction, persons with reduced swallowing function, and persons withreduced chewing function.(B-I-10) The additive for a composition for intraoral use or oral intakeaccording to any one of (B-I-1) to (B-I-9), which is an additive forpreparing a composition for intraoral use or oral intake in the form ofa gel having at least one of the following physical properties (1) and(2), or in the form of a sol having the following physical property (3):(1) fracture strain: 0.3 to 0.8;(2) hardness: 500 to 500,000 N/m²; and(3) viscosity: 0.006 to 0.6 Pa·s.(B-I-11) The additive for a composition for intraoral use or oral intakeaccording to any one of (B-I-1) to (B-I-10), which is used for one ofthe following (a) to (c):

(a) a salivator that imparts a salivation-promoting effect to acomposition for intraoral use or oral intake:

the salivator can be preferably used for preparing a composition forintraoral use or oral intake (a food or beverage, a pharmaceuticalproduct), the composition being for a person having reduced salivationfunction (a person with reduced salivation function);

(b) a swallowing-assisting agent that imparts an easy-to-swallowproperty to the composition for oral intake:

the swallowing-assisting agent can be preferably used for preparing acomposition for oral intake (a food or beverage, a pharmaceuticalproduct), the composition being for a person having reduced swallowingfunction (a person with reduced deglutition function); and

(c) a chewing-assisting agent that imparts an easy-to-chew property to acomposition for oral intake:

the chewing-assisting agent can be preferably used to prepare acomposition for oral intake (a food or beverage, a pharmaceuticalproduct), the composition being for a person having reduced chewingfunction (a person with reduced mastication function).

(B-II) Composition for Intraoral Use or Oral Intake, and Method forPreparation Thereof

(B-II-1) A composition for intraoral use or oral intake comprising theadditive for a composition for intraoral use or oral intake according toany one of (B-I-1) to (B-I-11).(B-II-2) The composition for intraoral use or oral intake according to(B-II-1), which is a food or beverage, or a pharmaceutical product.(B-II-3) The composition for intraoral use or oral intake according to(B-II-1) or (B-II-2), which is a food or beverage or a pharmaceuticalproduct ingested by or administered to at least one person selected fromthe group consisting of persons with reduced salivation function,persons with reduced swallowing function, and persons with reducedchewing function.(B-II-4) The composition for intraoral use or oral intake according toany one of (B-II-1) to (B-II-3), which is a food or beverage for healthypersons whose mouth is in a dry state.

The mouth in a dry state is not particularly limited. Examples includethe mouth in a dry state on exercising, bathing, waking, etc.

(B-II-5) The composition for intraoral use or oral intake according toany one of (B-II-1) to (B-II-4), which is a food or beverage or apharmaceutical product for intraoral use or oral intake that is in theform of a gel having at least one of the following physical properties(1) and (2), or in the form of a sol having the following physicalproperty (3):(1) fracture strain: 0.3 to 0.8(2) hardness: 500 to 500,000 N/m²(3) viscosity: 0.006 to 0.6 Pa·s.(B-II-6) A method for preparing the composition for intraoral use ororal intake according to any one of (B-II-1) to (B-II-5), comprisingincorporating enzymatically modified isoquercitrin and a thickeningpolysaccharide, or the additive for a composition for intraoral use ororal intake according to any one of (B-I-1) to (B-I-11) into a food orbeverage or a pharmaceutical product for intraoral use or oraladministration each having a water content of 60 mass % or more.

(B-III) Various Applications of Enzymatically Modified Isoguercitrin

(B-III-1-1) A method for enhancing the salivation-promoting effect ofenzymatically modified isoquercitrin, the method being characterized byusing a thickening polysaccharide with the enzymatically modifiedisoquercitrin.(B-III-1-2) The enhancement method according to (B-III-1-1), wherein thethickening polysaccharide is at least one member selected from the groupconsisting of xanthan gum, locust bean gum, guar gum, tara gum,deacylated gellan gum, highly acylated gellan gum, pectin, alginates,gelatin, agar, psyllium seed gum, and carrageenan.(B-III-1-3) The enhancement method according to (B-III-1-1) or(B-III-1-2), wherein the thickening polysaccharide is used in aproportion of 0.2 to 500 parts by mass per part by mass of theenzymatically modified isoquercitrin.(B-III-1-4) The enhancement method according to any one of (B-III-1-1)to (B-III-1-3), comprising forming a gel having at least one of thefollowing physical properties (1) and (2), or a sol having the followingphysical property (3) by using the thickening polysaccharide with theenzymatically modified isoquercitrin:(1) fracture strain: 0.3 to 0.8;(2) hardness: 500 to 500,000 N/m²; and(3) viscosity: 0.006 to 0.6 Pa·s.(B-III-1-5) The enhancement method according to (B-III-1-4) comprisingforming a sol by using the thickening polysaccharide in a proportion of0.2 to 400 parts by mass, preferably 0.3 to 350 parts by mass, and morepreferably 0.4 to 300 parts by mass, per part by mass of theenzymatically modified isoquercitrin.(B-III-1-6) The enhancement method according to (B-III-1-4), comprisingforming a gel by using the thickening polysaccharide in a proportion of1 to 500 parts by mass, preferably 2 to 450 parts by mass, and morepreferably 2.5 to 350 parts by mass, per part by mass of theenzymatically modified isoquercitrin.(B-III-1-7) The enhancement method according to any one of (B-III-1-1)to (B-III-1-4), comprising preparing a processed grain food or beverage,wherein the processed grain food or beverage contains the thickeningpolysaccharide in a proportion of 0.01 to 3000 parts by mass, preferably0.05 to 2000 parts by mass, and more preferably 0.1 to 1200 parts bymass, per part by mass of the enzymatically modified isoquercitrin.(B-III-2-1) A method for promoting salivation in a person with reducedsalivation function, comprising allowing a composition for intraoral useor oral intake comprising enzymatically modified isoquercitrin and athickening polysaccharide to be orally administered to or ingested bythe person with reduced salivation function.(B-III-2-2) The salivation-promoting method according to (B-III-2-1),wherein the thickening polysaccharide is at least one member selectedfrom the group consisting of xanthan gum, locust bean gum, guar gum,tara gum, deacylated gellan gum, highly acylated gellan gum, pectin,alginates, gelatin, agar, psyllium seed gum, and carrageenan.(B-III-2-3) The salivation-promoting method according to (B-III-2-1) or(B-III-2-2), wherein the composition for intraoral use or oral intakecomprises the thickening polysaccharide in a proportion of 0.2 to 500parts by mass per part by mass of the enzymatically modifiedisoquercitrin.(B-III-2-4) The salivation-promoting method according to (B-III-2-1) or(B-III-2-2), wherein the composition for intraoral use or oral intake isin the form of a sol, and comprises the thickening polysaccharide in aproportion of 0.2 to 400 parts by mass, preferably 0.3 to 350 parts bymass, and more preferably 0.4 to 300 parts by mass, per part by mass ofthe enzymatically modified isoquercitrin.(B-III-2-5) The salivation-promoting method according to (B-III-2-4),wherein the composition for intraoral use or oral intake is in the formof a gel, and contains the thickening polysaccharide in a proportion of1 to 500 parts by mass, preferably 2 to 450 parts by mass, and morepreferably 2.5 to 350 parts by mass, per part by mass of theenzymatically modified isoquercitrin.(B-III-2-6) The salivation-promoting method according to (B-III-2-4),wherein the composition for intraoral use or oral intake is a processedgrain food or beverage, and contains the thickening polysaccharide in aproportion of 0.01 to 3000 parts by mass, preferably 0.05 to 2000 partsby mass, and more preferably 0.1 to 1200 parts by mass, per part by massof the enzymatically modified isoquercitrin.(B-III-2-7) The salivation-promoting method according to any one of(B-III-2-1) to (B-III-2-6), wherein the composition for intraoral use ororal intake is a food or beverage or a pharmaceutical product.(B-III-2-8) The salivation-promoting method according to any one of(B-III-2-1) to (B-III-2-7), wherein the composition for intraoral use ororal intake is a food or beverage, or a pharmaceutical product in theform of a gel having at least one of the following physical properties(1) and (2), or in the form of a sol having the following physicalproperty (3):(1) fracture strain: 0.3 to 0.8;(2) hardness: 500 to 500,000 N/m²; and(3) viscosity: 0.006 to 0.6 Pa·s.(B-III-3-1) A composition for intraoral use or oral intake comprisingenzymatically modified isoquercitrin and a thickening polysaccharide,the composition being used for a person with reduced salivation functionto ameliorate reduction in saliva secretion or promote saliva secretion.(B-III-3-2) The composition for intraoral use or oral intake accordingto (B-III-3-1), wherein the thickening polysaccharide is at least onemember selected from the group consisting of xanthan gum, locust beangum, guar gum, tara gum, deacylated gellan gum, highly acylated gellangum, pectin, alginates, gelatin, agar, psyllium seed gum, andcarrageenan.(B-III-3-3) The composition for intraoral use or oral intake accordingto (B-III-3-1) or (B-III-3-2), wherein the composition for intraoral useor oral intake contains the thickening polysaccharide in a proportion of0.2 to 500 parts by mass per part by mass of the enzymatically modifiedisoquercitrin.(B-III-3-4) The composition for intraoral use or oral intake accordingto (B-III-3-1) or (B-III-3-2), which is in the form of a sol andcontains the thickening polysaccharide in a proportion of 0.2 to 400parts by mass, preferably 0.3 to 350 parts by mass, and more preferably0.4 to 300 parts by mass, per part by mass of the enzymatically modifiedisoquercitrin.(B-III-3-5) The composition for intraoral use or oral intake accordingto (B-III-3-1) or (B-III-3-2), which is in the form of a gel andcontains the thickening polysaccharide in a proportion of 1 to 500 partsby mass, preferably 2 to 450 parts by mass, and more preferably 2.5 to350 parts by mass, per part by mass of the enzymatically modifiedisoquercitrin.(B-III-3-6) The composition for intraoral use or oral intake accordingto any one of (B-III-3-1) to (B-III-3-5), wherein the composition forintraoral use or oral intake is a processed grain food or beverage, andcontains the thickening polysaccharide in a proportion of 0.01 to 3000parts by mass, preferably 0.05 to 2000 parts by mass, and morepreferably 0.1 to 1200 parts by mass, per part by mass of theenzymatically modified isoquercitrin.(B-III-3-7) The composition for intraoral use or oral intake accordingto any one of (B-III-3-1) to (B-III-3-6), which is a food or beverage ora pharmaceutical product for intraoral use or oral intake.(B-III-3-8) The composition for intraoral use or oral intake accordingto any one of (B-III-3-1) to (B-III-3-7), which is a food or beverage ora pharmaceutical product in the form of a gel having at least one of thefollowing physical properties (1) and (2), or in the form of a solhaving the following physical property (3):(1) fracture strain: 0.3 to 0.8;(2) hardness: 500 to 500,000 N/m²; and(3) viscosity: 0.006 to 0.6 Pa·s.

Advantageous Effects of Invention

Intake or administration of the salivator of the present invention to ahuman can promote saliva secretion in the human. Intake oradministration of the salivator to a human with reduced salivationfunction can ameliorate the reduction of saliva secretion in the human.Further, promoting salivation by using the salivator of the presentinvention can enhance a self-cleaning effect in the mouth, and can alsoprevent various negative effects caused by reduction in saliva secretion(such as dry mouth, unpleasant sensation in the mouth, taste disorder,halitosis, dental caries, periodontal diseases, infection of mucosa, andlike mouth dysfunctions; difficulty in conversation and utterance;etc.). Further, the salivator of the present invention, which promotessalivation, can facilitate swallowing by humans with difficulty inswallowing due to reduced saliva secretion.

Further, since the salivator of the present invention uses as an activeingredient enzymatically modified isoquercitrin, which has a history ofusage as a food, the salivator is highly safe, and can be preferablyused as a composition for intraoral use or oral intake that iscontinuously used in the mouth or orally administered (e.g.,pharmaceutical products, quasi-drugs, foods and beverages (includingfunctional foods and beverages, and health foods and beverages)). Thesalivator of the present invention can be used as a pharmaceuticalproduct for intraoral use or oral administration, and can be preferablyused as a functional food or beverage or a health food or beverage inalternative medicine, or complementary and alternative medicine.

The additive for a composition for intraoral use or oral intake of thepresent invention can impart a salivation-promoting effect,easy-to-swallow property, and/or easy-to-chew property to a compositionfor intraoral use or oral intake, such as a food or beverage or apharmaceutical product. Therefore, the additive can be preferably usedto prepare a food or beverage or a pharmaceutical product for intraoraluse or oral administration, which is ingested by or administered to aperson with reduced salivation function, a person with reducedswallowing function, or a person with reduced chewing function. Inparticular, since the additive for a composition for intraoral use ororal intake of the present invention that contains a thickeningpolysaccharide in a proportion of 0.2 to 500 parts by mass per part bymass of the enzymatically modified isoquercitrin hardly affectspalatability (taste, smell, etc.), this additive can be used forpreparing a composition for intraoral use or oral intake without severerestrictions on the amount to be added.

Further, the composition for intraoral use or oral intake of the presentinvention, which contains the additive for a composition for intraoraluse or oral intake, has a salivation-promoting effect, easy-to-swallowproperty and/or easy-to-chew property; and can be preferably used as afood or beverage or a pharmaceutical product for intraoral use or oraladministration that is ingested by or administered to a person withreduced salivation function, a person with reduced swallowing function,or a person with reduced chewing function.

According to the method of the present invention, the use of athickening polysaccharide with enzymatically modified isoquercitrin canenhance the salivation-promoting effect of the enzymatically modifiedisoquercitrin. Accordingly, when an oral composition containing athickening polysaccharide in addition to enzymatically modifiedisoquercitrin is ingested by or administered to a subject with reducedsalivation function, saliva secretion is promoted in the subject,thereby ameliorating reduction in saliva secretion.

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1 is a graph showing the measurement results ofsalivation-promoting effects in Experimental Example 1. The amount ofsaliva secreted is shown as a relative value, with the amount of salivasecreted by ingestion of water being set as 1 (the same applies in FIG.2).

FIG. 2 is a graph showing the measurement results ofsalivation-promoting effects in Experimental Example 2.

FIG. 3 is a graph showing salivation-promoting effects of solcompositions for intraoral use or oral intake in Experimental Example 4(Control sample 4, and Test samples 4-1 to 4-5). The xanthan gum (XG)content of each composition for intraoral use or oral intake (mass %) isalso shown on the abscissa. The amount of saliva secreted is shown as arelative value, with the amount of saliva secreted by intake of waterbeing set as 1.

FIG. 4 is a graph showing the salivation-promoting effects of solcompositions for intraoral use or oral intake in Experimental Example 5(Test samples 5-1 to 5-5). The molarity (μM) of the content ofenzymatically modified isoquercitrin in each composition for intraoraluse or oral intake in terms of rutin (the content in terms of rutin) isalso shown on the abscissa. The amount of saliva secreted is shown as arelative value, with the amount of saliva secreted by intake of waterbeing defined as 1.

FIG. 5 shows a graph showing the salivation-promoting effect of gelcompositions for intraoral use or oral intake in Experimental Example 6(Control samples 6-1 to 6-5, and Test samples 6-1 to 6-5). The amount ofsaliva secreted is a relative value, with the amount of saliva secretedby intake of water being defined as 1.

FIG. 6 is a graph showing the saliva secretion-promoting effects of gelcompositions for intraoral use or oral intake in Experimental Example 7(Control sample 7, and Test samples 7-1 to 7-5). The molarity (μM) ofthe content of enzymatically modified isoquercitrin in each compositionfor intraoral use or oral intake in terms of rutin (the content in termsof rutin) is also shown on the abscissa. The amount of saliva secretedis a relative value, with the amount of saliva secreted by intake ofwater being defined as 1.

DESCRIPTION OF EMBODIMENTS (A-I) Salivator (A-I-1) EnzymaticallyModified Isoquercitrin

The salivator of the present invention is characterized in that thepromoter contains enzymatically modified isoquercitrin (English name:enzymatically modified isoquercitrin) as an active ingredient. Theenzymatically modified isoquercitrin contains α-glucosyl isoquercitrinrepresented by the following formula as a main component, and is alsocalled sugar-transferred isoquercitrin.

In the above formula, n represents an integer of 0 to 10.

α-Glucosyl isoquercitrin contained in the enzymatically modifiedisoquercitrin may be one compound wherein n is an integer of 0 to 10, ora mixture of two or more compounds wherein n is an integer of 0 to 10.Preferably, the α-glucosyl isoquercitrin is a mixture, and morepreferably is a mixture of two or more compounds wherein n is an integerof 0 to 6. α-Glucosyl isoquercitrin wherein n is 0 is also referred toas isoquercitrin. In the present invention, an enzymatically modifiedisoquercitrin containing α-glucosyl isoquercitrin in an amount of 60mass % or more in terms of rutin is preferably used.

The α-glucosyl isoquercitrin content of enzymatically modifiedisoquercitrin is shown in terms of rutin because rutin and α-glucosylisoquercitrin have the same molar extinction coefficient at a wavelengthof 351 nm, and rutin is more readily available than α-glucosylisoquercitrin. Therefore, in this technical field, it is common practiceto quantify the α-glucosyl isoquercitrin content of enzymaticallymodified isoquercitrin in terms of rutin by UV-visible absorbancespectroscopy using rutin as a standard sample.

Specifically, the α-glucosyl isoquercitrin content of enzymaticallymodified isoquercitrin can be calculated in terms of rutin by thefollowing quantification method described in the “Enzymatically ModifiedIsoquercitrin” column in The Japanese Standards of Food Additives, 8thedition (The Ministry of Health, Labour and Welfare).

Quantification

(i) The target enzymatically modified isoquercitrin (target sample) isdried, and about 0.05 g of enzymatically modified isoquercitrin isaccurately weighed and dissolved in water to make the total volumeexactly 100 ml. Filtration may be performed, if necessary. 4 ml of thissolution is accurately measured, and a phosphoric acid solution (anaqueous solution prepared by dissolving 1 g of phosphoric acid in waterto make a total volume of 1000 ml; the same applies hereinafter) isadded to make the total volume 100 ml, thus preparing a test liquid.(ii) Separately, rutin for quantification is dried at 135° C. for 2hours. About 0.05 g of the rutin is accurately weighed and dissolved inmethanol to make the total volume exactly 100 ml. 4 ml of this solutionis accurately measured, and the phosphoric acid solution is added tomake the total volume exactly 100 ml, thus preparing a standard liquid.(iii) The absorbance of the test liquid (At) and standard liquid (As) ata wavelength of 351 nm is measured by UV-visible absorbance spectroscopyusing the phosphoric acid solution as a control. The α-glucosylisoquercitrin content in terms of rutin is calculated by the followingformula.

α-Glycosyl isoquercitrin content (as rutin (C₂₇H₃₀O₆))=(Amount of rutinfor quantification sampled (g)/Amount of Test Sample sampled(g)×(At/As)×100(mass %))  [Math. 1]

Enzymatically modified isoquercitrin can be generally prepared by addingglucose to a mixture of isoquercitrin and starch or dextrin by usingcyclodextrin glucosyltransferase. Isoquercitrin is generally obtained byenzymatic degradation of rutin. Isoquercitrin can also be obtained byother known methods (such as degradation of rutin, extractive isolationfrom a plant, and glycosidation of quercetin). Conveniently, thepharmaceutical preparation containing enzymatically modifiedisoquercitrin is commercially available. Examples of such commerciallyavailable products include “San Emiq No. 1” produced by San-Ei GenF.F.I., Inc. “San Emiq” is a registered trademark of San-Ei Gen F.F.I.,Inc. The enzymatically modified isoquercitrin contained in “San Emiq No.1” is a mixture of two or more compounds represented by the aboveformula wherein n is selected from 0 to 6. San Emiq No. 1 containsα-glucosyl isoquercitrin as a main component in an amount of 60 mass %or more in terms of rutin. “San Emiq No. 1” contains α-glucosylisoquercitrin in an amount of 10 mass % in terms of rutin by the abovequantification method, and further contains dextrin as anothercomponent.

The salivator of the present invention may be any promoter containingenzymatically modified isoquercitrin, as long as it provides asalivation-promoting effect. The enzymatically modified isoquercitrincontent is not particularly limited, and can be appropriately selectedfrom the range of 0.001 to 0.5 mass % as α-glucosyl isoquercitrin (interms of rutin [C₂₇H₃₀O₁₆]). In this specification, the enzymaticallymodified isoquercitrin content is shown as the α-glucosyl isoquercitrincontent (in terms of rutin [C₂₇H₃₀O₁₆]) (mass %), unless otherwisespecified. Accordingly, in the present invention (this specification),“1 part by mass of enzymatically modified isoquercitrin” means that theamount of α-glucosyl isoquercitrin contained in enzymatically modifiedisoquercitrin is 1 part by mass in terms of rutin [C₂₇H₃₀O₁₆].

(A-I-2) Polysaccharides for Thikening

The salivator of the present invention may contain a thickeningpolysaccharide in addition to enzymatically modified isoquercitrin.

As shown in the Experimental Examples below, a salivator containing athickening polysaccharide in addition to enzymatically modifiedisoquercitrin can provide a higher salivation-promoting effect than thecorresponding salivator not containing a thickening polysaccharide.

The thickening polysaccharide to be used in the present invention is anedible thickening polysaccharide that is allowed to be used in a food orbeverage or a pharmaceutical product for oral administration. Examplesof thickening polysaccharides include xanthan gum, galactomannan (e.g.,locust bean gum, guar gum, tara gum, etc.), deacylated gellan gum,highly acylated gellan gum, carrageenan (e.g., kappa-carrageenan,iota-carrageenan, lambda-carrageenan, etc.), tamarind seed gum,glucomannan, psyllium seed gum, macrophomopsis gum, agar, gelatin,pectin (e.g., HM pectin, LM pectin, etc.), alginic acid, alginates(alginic acid salts) (e.g., sodium alginate, potassium alginate, calciumalginate, etc.), pullulan, curdlan, gum tragacanth, ghatti gum, gumarabic, arabinogalactan, karaya gum, furcellaran, chitin, welan gum,celluloses (e.g., sodium carboxymethyl cellulose, carboxymethylcellulose calcium, carboxymethyl cellulose, hydroxypropyl cellulose,hydroxypropyl methylcellulose, hydroxypropyl ethylcellulose,hydroxyethylcellulose, hydroxymethylcellulose, ethyl cellulose, methylcellulose, fermented cellulose, crystalline cellulose, etc.), starches(e.g., starch, sodium carboxymethyl starch, carboxymethyl starch,hydroxypropyl starch, gelatinized starch, phosphoric acid-crosslinkedstarch, octenylsuccinic acid starch, starch acetate, etc.), dextrins(e.g., polydextrose, indigestible dextrin, etc.), soybeanpolysaccharides, and the like.

In the present invention, among the thickening polysaccharides, at leastone member selected from the group consisting of xanthan gum, locustbean gum, guar gum, tara gum, deacylated gellan gum, highly acylatedgellan gum, pectin, alginates, gelatin, agar, psyllium seed gum, andcarrageenan is preferable. More preferably, the thickeningpolysaccharide is at least one member selected from the group consistingof xanthan gum, locust bean gum, guar gum, deacylated gellan gum, highlyacylated gellan gum, pectin, and carrageenan. Particularly preferably,the thickening polysaccharide is at least one member selected from thegroup consisting of xanthan gum, pectin, and carrageenan. Thesethickening polysaccharides can be used singly, or in a combination oftwo or more. The combination of two or more thickening polysaccharidesis not particularly limited. Examples include a combination of xanthangum and guar gum; a combination of xanthan gum and locust bean gum; acombination of xanthan gum and carrageenan; a combination of xanthangum, guar gum, and locust bean gum; and a combination of deacylatedgellan gum and highly acylated gellan gum. Further, at least one memberselected from the group consisting of these thickening polysaccharidescan be used in combination with at least one member selected from thegroup consisting of the thickening polysaccharides described above.

The proportion of the thickening polysaccharide to the enzymaticallymodified isoquercitrin in the salivator of the present invention can beusually selected from the range of 0.2 to 500 parts by mass per part bymass of the enzymatically modified isoquercitrin (in terms of rutin; thesame applies hereinafter). For example, when the salivator of thepresent invention is in the form of a solid, such as a tablet, granuleor powder (powdered medicine), or dry syrup, the proportion of thethickening polysaccharide may be, for example, 0.2 to 500 parts by mass,preferably 0.3 to 400 parts by mass, and more preferably 0.4 to 350parts by mass, per part by mass of the enzymatically modifiedisoquercitrin. When the salivator of the present invention is in theform of a paste, the proportion of the thickening polysaccharide may be,for example, 0.2 to 500 parts by mass, preferably 0.3 to 400 parts bymass, and more preferably 0.4 to 350 parts by mass, per part by mass ofthe enzymatically modified isoquercitrin. When the salivator of thepresent invention is in the form of a liquid, the proportion of thethickening polysaccharide may be, for example, 0.2 to 400 parts by mass,preferably 0.3 to 350 parts by mass, and more preferably 0.3 to 300parts by mass, per part by mass of the enzymatically modifiedisoquercitrin. When the salivator of the present invention is in theform of a gel (jelly), the proportion of the thickening polysaccharidemay be, for example, 1 to 500 parts by mass, and preferably 2 to 450parts by mass, and more preferably 2.5 to 350 parts by mass, per part bymass of the enzymatically modified isoquercitrin.

As described above, the proportion of the thickening polysaccharidecontained in the salivator of the present invention varies according tothe form of the salivator. For example, when the form of the salivatoris a solid form such as a tablet, chewable agent, lozenge, granule,powder (powdered medicine), dry syrup, film, or stick-like preparation,the proportion of the thickening polysaccharide can be appropriatelyselected from the range of 1 mass % or more to 99.9 mass % or less. Theproportion of the thickening polysaccharide is preferably 3 to 90 mass%, and more preferably 5 to 80 mass % more. When the form of thesalivator is a paste or liquid form (including a syrup, health drink,liquid, emulsion, oil, and spray), the proportion of the thickeningpolysaccharide can be appropriately selected from the range of 0.02 to30 mass %, preferably 0.02 to 10 mass %, and more preferably 0.02 to 8mass %. When the salivator is in the form of a gel, the proportion ofthe thickening polysaccharide per part by mass of the enzymaticallymodified isoquercitrin may be appropriately selected from the range of0.02 to 10 mass %. Preferably, the proportion of the thickeningpolysaccharide is 0.02 to 8 mass %, and more preferably 0.02 to 6 mass.

(A-I-3) Other Components

The salivator of the present invention may contain any edible componentsin addition to the above components, as long as the effect of thepresent invention is not impaired.

Examples of edible components include edible metal salts, excipients,organic acids, coloring agents, amino acids (e.g., glycine, arginine,lysine, alanine, glutamic acid, histidine, threonine, asparagine,aspartic acid, phenylalanine, leucine, valine, serine, tyrosine,isoleucine, methionine, etc.), nutrients (including vitamins andminerals), antioxidants, preservatives, antimicrobial agents,bacteriostatic agents, plant extracts (e.g., tea extracts, coffeeextracts, cocoa extracts, etc.), fruit juices (e.g., orange, grape,apple, peach, pineapple, tomato, strawberry, etc.), sweeteners (e.g.,sugars such as sucrose, isomerized sugar, lactose, maltose, glucose,fructose, invert sugar, starch syrup, powder starch syrup, reducedmaltose syrup, honey, trehalose, palatinose, and D-xylose; sugaralcohols such as xylitol, sorbitol, maltitol, and erythritol;high-sweetness sweeteners such as sodium saccharin, cyclamate or saltsthereof, potassium acesulfame, thaumatin, aspartame, sucralose, alitame,neotame, stevia extracts (e.g., stevioside), and Momordica grosvenoriextract (e.g., mogroside)), flavors, and the like.

The edible metal salt is used to improve solubility of the thickeningpolysaccharide in water, or enhance thickening and gelling functions.The kind of edible metal salt is not particularly limited. Preferableexamples include sodium salts (e.g., sodium chloride and sodiumcitrate), potassium salts (e.g., potassium chloride, potassium citrate,etc.), calcium salts (e.g., calcium chloride, calcium citrate, etc.),magnesium salts (e.g., magnesium chloride, etc.), and the like. When anedible metal salt is used, the proportion of the edible metal salt inthe salivator of the present invention may be, for example, usually 0.1to 15 mass %, and preferably 0.5 to 10 mass %, regardless of the form ofthe salivator (solid, semi-solid, or liquid form).

To produce the salivator in a form for intraoral use or oral intake, orstabilize the salivator, various carriers and additives pharmaceuticallyacceptable for oral administration may be incorporated (see, forexample, a pharmacopeia, or the “Japanese Pharmaceutical ExcipientsDirectory” (published by Yakuji Nippo, Limited)).

Examples of such carriers or additives include excipients such asmonosaccharides (e.g., glucose, galactose, fructose, etc.),disaccharides (e.g., sucrose, saccharose, lactose, maltose, trehalose,etc.), sugar alcohols (e.g., xylitol, sorbitol, mannite, etc.),oligosaccharide, starches (e.g., corn starch, partially gelatinizedstarch, etc.), starch hydrolysates (e.g., dextrin, powdered starchsyrup, etc.), cellulose or cellulose derivatives (e.g., crystallinecellulose, low-substituted hydroxypropyl cellulose, carmellose sodium,etc.), and talc; binders such as starch, gelatinized starch, gelatin,gum arabic, dextrin, methyl cellulose, ethyl cellulose,polyvinylpyrrolidone, hydroxypropyl methylcellulose, hydroxypropylcellulose, and carboxymethyl cellulose or salts thereof; disintegrantssuch as calcium carbonate, crospovidone, starch, carboxymethyl cellulosecalcium, low-substituted hydroxypropyl cellulose, carboxymethyl starch,crystalline cellulose, and agar; lubricants such as magnesium stearate,talc, polyethylene glycol, and silicic acid anhydride; suspending agentssuch as Polysorbate 80, polyoxyethylene hydrogenated castor oil, andPluronic; coating agents such as saccharose, talc, precipitated calciumcarbonate, gelatin, gum arabic, pullulan, carnauba wax, andhydroxypropylmethyl phthalate; corrigents such as saccharose, glucose,saccharin sodium, sorbitol, citric acid, and aspartame; and the like. Aslong as the effect of the present invention is not impaired, thefollowing additives may also be used in addition to the abovecomponents: components usually acceptable as additives forpharmaceutical products, such as stabilizing agents, surfactants,plasticizers, capsule films, solubilizers, reducing agents, buffers,sweetening agents, bases, volatilization adjuvants, absorptionenhancers, adsorbents, synergists, curing agents, antioxidants,brightening agents, perfumes, potency enhancers, coating agents,supports, prolonging agents, moistening agents, moisture regulators,fillers, defoaming agents, algefacients, eating stimulants, bonds,potentiators, chewable agents, antistatic agents, flavors, coloringagents, sugar-coating agents, tonicity agents, softeners, emulsifiers,combustion agents, adhesives, adhesion enhancers, viscosity modifiers,inflammation suppressants, exothermic agents, foaming agents, pHadjusters, skin protectants, flotation agents, dispersants, propellants,fragrances, antirust agents, desiccants, release control membranes,antiseptic agents, scavengers, preservatives, soothing agents,attractants, dissolving agents, dissolving adjuvants, solvents, liners,mold release agents, and fluidizers; components acceptable as foodadditives, such as sweeteners, coloring agents, preservatives,thickeners, gelling agents, starch adhesives, antioxidants, colorformers, bleaching agents, antifungal agents, emulsifiers, leaveningagents, seasoning agents, sour tastes, bitter tastes, gloss agents, gumbases, nutrition fortifiers, and agents for production; any componentssuch as flavors. Components that have saliva secretion-promotingeffects, such as spilanthol, may also be added.

(A-I-4) Form, Preparation Method, Function, Use, Etc., of the Salivator

The form of the salivator of the present invention is not limited aslong as the salivator of the present invention comprises at least theenzymatically modified isoquercitrin alone, or the enzymaticallymodified isoquercitrin and a thickening polysaccharide. For example, theform of the salivator may be a solid (e.g., tablets, chewable agents,lozenges, pills, granules, powders (powdered medicine), dry syrups,films, stick-shaped preparations, etc.), a semi-solid (e.g., gels,pastes, etc.), a liquid (e.g., syrups, health drinks, liquids,emulsions, oils, sprays, etc.), and the like.

The salivator in a solid or semi-solid form is not particularly limitedas long as it is in a form for use in the mouth (a form for intraoraluse), or in a form for use by oral administration (a form for oraladministration). The salivator may be, for example, in the form of atablet, chewable agent, lozenge, pill, granule, powder (powderedmedicine), dry syrup, film, stick-shaped preparation, gel, or paste.When used, the tablet, pill, granule, or powder (powdered medicine), drysyrup, etc., may be added to drinking water or a food or beverage; anddissolved or dispersed and mixed therein, and then administered(ingested).

The salivator of the present invention can be prepared in accordancewith the form by known methods. For example, the salivator in the formof a powder (powdered medicine) or dry syrup can be prepared bypowder-mixing enzymatically modified isoquercitrin alone, orenzymatically modified isoquercitrin and a thickening polysaccharidewith an excipient. Alternatively, the salivator in the form of a powdercan also be prepared by drying (e.g., spray-drying, freeze-drying, etc.)a liquid containing enzymatically modified isoquercitrin alone, orenzymatically modified isoquercitrin and a thickening polysaccharide.The salivator in the form of granules can be prepared by granulating thepowder mixture. Alternatively, the salivator in the form of granules canalso be prepared by spraying an aqueous solution of enzymaticallymodified isoquercitrin as a binder solution over a powder thickeningpolysaccharide. The salivator in the form of tablets can be prepared bytableting the powder or granular salivator into tablets using atableting machine. The salivator in the form of a liquid can be preparedby adding enzymatically modified isoquercitrin alone, or enzymaticallymodified isoquercitrin and a thickening polysaccharide to a solvent (forexample, ethanol or water, or a mixture thereof, preferably water suchas purified water, ion exchange water, distilled water, or physiologicalsaline); and preferably further mixing (for example, mixing bystirring). The salivator in the form of a liquid can be prepared as anemulsion or an oil by further adding a surfactant and/or a dispersantand a liposoluble solvent (for example, an oil solvent (e.g., apharmaceutical oil solvent for dissolving a liposoluble medicament,edible oil, etc.), and preferably further mixing (for example, mixing bystirring) or performing homogenization treatment by using ahigh-pressure homogenizer etc. at the stage of preparing the salivatorin the form of a liquid.

The gel salivator can be prepared by adding to a solvent (ethanol orwater, or a mixture thereof, preferably water such as purified water,ion exchange water, or distilled water, or physiological saline)enzymatically modified isoquercitrin and a thickening polysaccharidethat contributes to gelling, and heating until the thickeningpolysaccharide is homogeneously dissolved (dispersed) (the heatingtemperature depends on the polysaccharide to be added and may be, forexample, 40 to 100° C.), followed by cooling. In this case, examples ofpolysaccharides that contribute to gelling include xanthan gum, locustbean gum, highly acylated gellan gum, gelatin, agar, and carrageenan.Alternatively, after enzymatically modified isoquercitrin and athickening polysaccharide, which contributes to gelling, are added to asolvent (ethanol or water, or a mixture thereof, preferably purifiedwater, ion exchange water, or distilled water, or physiological saline)and the resulting mixture is mixed and dissolved (dispersed) (at anyappropriate temperature), the resulting solution may be gelled by addingan edible metal salt. In this case, examples of thickeningpolysaccharides that contribute to gelling include deacylated gellangum, pectin, alginates, and carrageenan. The edible metal salt is notparticularly limited. Preferable examples of edible metal salts includesodium salts (e.g., sodium chloride, sodium citrate, etc.), potassiumsalts (e.g., potassium chloride, potassium citrate, etc.), calcium salts(e.g., calcium chloride, calcium citrate, etc.), magnesium salts (e.g.,magnesium chloride etc.), and the like. The edible metal salt, whenused, is preferably incorporated into the composition for intraoral useor oral intake of the present invention in a proportion of 0.00001 to 15mass %, and preferably 0.00002 to 10 mass %.

When the salivator is in the form of a liquid, the viscosity may beadjusted to 6 mPa·s or more, preferably 6 to 600 mPa·s, by using athickener, if necessary.

The viscosity herein refers to the viscosity determined under thefollowing measurement conditions using a fluid rheometer (for example,ARES-LS1 produced by TA Instruments).

Measurement Conditions

-   -   Measurement temperature: 20° C.    -   Geometry: cone-and-plate with a diameter of 50 mm and a gap of        0.051 mm    -   Shear rate: 100 s⁻¹

The “viscosity” in this specification means the viscosity determinedunder these conditions.

The thickener is not particularly limited. Examples include thickeningpolysaccharides as described above; monosaccharides such as glucose andfructose; disaccharides such as sucrose, lactose, and trehalose;oligosaccharide consisting of three or more monosaccharides connectedtogether; polysaccharides such as starch, inulin, and polydextrose;starch syrup; sugar alcohols such as sorbitol, mannitol, maltitol,erythritol, lactitol, xylitol, and glycerol; and mixtures of saccharidessuch as molasses, honey, fructose-glucose liquid sugar, reduced maltosesyrup, reduced starch hydrolysate, and starch syrup (these may becollectively referred to as “saccharides”). These can be used alone, orin a combination of two or more. Preferably, the thickener is athickening polysaccharide.

The salivator in the form of a liquid of the present invention can beprovided in the form of a solution, spray, dropping, or ejection(including compositions for intraoral use, such as mouthwashes, liquiddentifrices, oral rinses, and oral sprays; and compositions for oraladministration, such as syrups), or formulated into health drinks. Thesalivator in various forms as described above can be used in the stateof being contained in various containers, such as bottles, pumps,sprays, tubes, cans, and jars.

The stick-shaped preparation can be directly applied to the lip or inthe mouth, and particularly to the tooth surface and gum. The shape ofthe stick-shaped preparation is not particularly limited as long as itis in a solid form that can be dissolved by saliva after application.The preparation can be formed into a cylindrical, square-pillar, or likeshape according to the purpose of use. The stick-shaped preparation ispreferably accommodated in an easily portable, appropriately shapedplastic container in such a manner that the preparation can be pushedout. When used, an appropriate amount of the preparation can be pushedout of the accommodation container, and applied to the lip or in themouth. Specifically, the preparation can be formed into the same shapeas lipsticks, lip creams, etc.

The pH of the salivator of the present invention is not limited. Ingeneral, the pH is preferably in the range of 3 to 9, more preferably3.5 to 8, and still more preferably 3.5 to 7.5. The salivator in theform of a solid or semi-solid form is usually preferably adjusted suchthat the salivator in the mouth after intake or administration has a pHin the range of 3 to 9. The pH in the mouth is preferably a pH in therange of 3.5 to 8, and more preferably a pH in the range of 3.5 to 7.5.

The salivator of the present invention is preferably prepared in such amanner that the amount of enzymatically modified isoquercitrin perintake is 0.1 to 250 mg, and more preferably to 0.4 to 100 mg. Thesalivator of the present invention can be used at any time when theamount of saliva decreases, or when an increase in saliva secretion isdesired (when or before the mouth is dried). Accordingly, the number ofadministrations of the salivator of the present invention per day is notparticularly limited. The salivator containing the above amount ofenzymatically modified isoquercitrin can be administered once or severaltimes a day, continuously or intermittently.

The salivator of the present invention has a saliva secretion-promotingfunction or saliva secretion-increasing function; and can be preferablyused for subjects with reduced saliva secretion, or subjects who feelreduced saliva secretion. Examples of subjects with reduced salivasecretion include patients with saliva hyposecretion or xerostomia; orhealthy persons whose mouth is in a dry state, for example, onexercising, bathing, or waking.

(A-I-5) Foods and Beverages Containing the Salivator

Foods and beverages having saliva secretion-promoting effects can beproduced by incorporating the salivator of the present invention intofoods or beverages. The timing of adding the salivator of the presentinvention to a food or beverage is not particularly limited. Thesalivator can be added, for example, in a step of producing a food orbeverage, or immediately before eating the food or drinking the beverageafter production. The food or beverage in which the salivator of thepresent invention is to be incorporated is not particularly limited.Examples include beverages such as milk beverages, lactobacillusbeverages, drink yogurts, soft drinks, near-water beverages, isotonicdrinks, carbonated beverages, fruit juice beverages, vegetablebeverages, fruit and vegetable beverages, alcoholic beverages, powderbeverages, concentrated drinks for dilution with water, coffeebeverages, shiruko (sweet red-bean soup with pieces of rice cake)beverage, black tea beverages, green tea beverages, barley teabeverages, hoji (roasted green) tea beverages, genmai (brown rice) teabeverages, oolong tea beverages, hatomugi (adlay) tea beverages, soba(buckwheat) tea beverages, dattan soba (tartary buckwheat) teabeverages, pu'er tea beverages, and smoothie beverages; puddings such ascustard pudding, milk pudding, chocolate pudding, soufflé pudding, andfruit juice-containing pudding; desserts such as jelly, gummi candy,Bavarian cream, mousse, yogurt, and multi-layer desserts; frozendesserts such as ice cream, ice milk, lacto ice, milk ice cream, fruitjuice-containing ice cream, soft-serve ice cream, ice pops, sherbet, andfrozen confections; gums (stick gum and sugar-coated gum granules) suchas chewing gum and bubble gum; chocolates such as marble chocolate andlike coating chocolates, strawberry chocolate, blueberry chocolate,melon chocolate, and like flavored chocolates; ramune (tablet candies);hard candies (including bonbons, butterballs, and marbles), soft candies(including caramel, nougat, gummi candy, and marshmallow), drops, taffy,and like caramels; baked confectioneries such as hard biscuits, cookies,macaroons, karinto (fried dough cake), okaki (cracker made fromglutinous rice), and senbei (cracker made from regular rice)(the aboveitems are confectioneries); soups such as miso soup, sumashi jiru (clearsoup), consonmm soup, potage soup, and vegetable soup; pickles such asasazuke (lightly pickled vegetables), soy sauce pickles, salt pickles,and miso pickles; sauces such as vinaigrette dressings, non-oildressings, ketchup, gravy, and sauce; jams such as strawberry jam,blueberry jam, marmalade, apple jam, apricot jam, and preserves; dessertsauces such as fruit sauce, syrup, and maple syrup; fruit wines such asred wine; processed fruits such as candied cherries, apricots, apples,strawberries, and peaches; processed meats such as ham, sausage, androast pork; ground marine products such as fish-meat ham, fish-meatsausage, ground fish meat, boiled fish paste, chikuwa (tubular fishcakes), hanpen (a cake of pounded fish), satsumaage (fried fish cakes),datemaki (mixed fish paste rolled omelet), and whale bacon; processedfarm products such as konjac, azuki bean, soybean curd (tofu), andfermented soybean; dairy-fat products such as butter, margarine, cheese,and whipped cream; pastas such as udon (noodles made from buckwheat),hiyamugi (cold wheat noodles), somen (thin wheat noodles), soba (noodlesmade from buckwheat), Chinese soba noodles, spaghetti, macaroni, ricenoodles, harusame (thin noodles made from bean starch), and wonton;baked goods such as breads, sweet buns, side dish breads, rolls, Frenchbreads, bagels, and croissants; flour-containing foods such as takoyvaki(grilled dumplings with bits of octopus), okonomiyaki (grilled spicypancakes with a wide variety of ingredients), crepe, shaomai (a steamedmeat dumpling), jiaozi (a Chinese-style dumpling with minced pork andvegetable stuffing), spring roll, wonton, and pizza; cakes such as largepancakes, pancakes, cheesecakes, chiffon cakes, soufflé cakes, chocolatecakes, fruit cakes, tarts, pies, cream puffs, and eclairs; Japanesesweets such as ohagi (Japanese rice cake wrapped with a sweet beanpaste), dumpling, bracken rice cake, kusamochi (a rice-flour dumplingmixed with mugwort), kudzu starch cake, manju (a steamed yeast bun withfilling), yokan (azuki bean jelly), mizuyokan (soft, sweet jellied beanpaste) anmitsu (mitsumame topped with a red bean jam), and glutinousrice-flour dumplings; grain staple foods such as cooked white rice,cooked brown rice, mugimeshi (rice cooked with barley), festive redrice, rice dumpling in bamboo leaves, and rice cakes; other varioustypes of side dishes and processed foods such as fu (dried bread-likepieces of wheat gluten) and denbu (mashed and seasoned fish). The foodsand beverages into which the salivator of the present invention is to beincorporated include concentrated liquid foods, enteral nutrients,thickened beverages, thickened liquid foods, nutrition supplement jelly,water-supplement jelly, semi-solid liquid food, liquid thickeners, andthe like. The “liquid thickener” refers to a liquid preparation used bybeing added to a food or beverage before eating or drinking in order tothicken the food or beverage.

By promoting saliva secretion and increasing the amount of salivasecreted, the salivator of the present invention enables subjects withreduced salivation to easily swallow and chew. In this sense, thesalivator of the present invention is also useful as aswallowing-assisting agent (a deglutition improver) or achewing-assisting agent (or a mastication improver). In this invention,“swallowing” or “deglutition” refers to swallowing down an object in themouth; and “chewing” or “mastication” refers to fragmenting an oralcomposition into small pieces in the mouth, or fully mixing an oralcomposition with saliva in the mouth while fragmenting the compositioninto small pieces. Finely cutting as used herein includes not onlycrunching an oral composition using the lower jaw and teeth, but alsosquashing an oral composition using the gums or tongue.

(A-II) Method for Promoting Saliva Secretion in Subject

As described above, the salivator of the present invention can promotesaliva secretion not only in healthy subjects but also in subjects withreduced salivation, or subjects who feel reduced saliva secretion.Therefore, the present invention provides a method for producing salivasecretion in these subjects.

This method can be performed by applying the salivator of the presentinvention to the mouth of the subject, or by oral administrationthereof. The application to the mouth can be suitably selected accordingto the form of the salivator. For example, when the salivator is in aliquid form such as a solution, spray, dropping, or ejection,application to the mouth may be, for example, mouth-rinsing,teeth-brushing, and gargle (gargling); or spraying into the mouth. Whenthe salivator is in the form of a solid chewable agent (including gum),the application may be, for example, mastication (chewing). When thesalivator is in a stick, gel, or paste (cream, ointment) form, forexample, application to the mouth can be used. Oral administration canbe performed by oral intake (administration) of the salivator in aliquid, semi-solid, or solid form (for example, a syrup, health drink,liquid, emulsion, oil, spray, gel, paste, tablet, chewable agent,lozenge, pill, granule, powder (powdered medicine), dry syrup, film, orstick-shaped preparation; or in the form of a syrup, drink, candy,jelly, gummi candy, edible film, or the like) according to the dosageform.

The timing of intake (administration) is not particularly limited. Thesalivator can be administered at any time when or before the mouth isdry. The amount of the salivator to be used is also not particularlylimited. The salivator is preferably administered (ingested) in anamount such that the enzymatically modified isoquercitrin contained inthe salivator is administered (ingested) in an amount of 0.1 to 250 mg,more preferably 0.4 to 100 mg. The number of times of administration ofthe salivator (number of times of intake) per day is not particularlylimited. The salivator containing the enzymatically modifiedisoquercitrin can be administered (ingested) in the above amount once aday or several times, continuously or intermittently, as describedabove.

The subjects with reduced salivation, for whom the method of the presentinvention is preferably used, include, for example, persons withhyposalivation or xerostomia; or healthy persons whose mouth is in a drystate on exercising, bathing, waking, etc. Examples of the method fordiagnosing reduction in saliva secretion include (1) methods formeasuring the amount of saliva produced at rest (the spitting method,the cotton-roll method), (2) a method for measuring the amount of salivasecreted upon stimulation (the Saxon method), (3) methods for measuringthe degree of oral mucosa moisture (the Periotron method, the filterpaper method, an intraoral moisture meter), (4) methods for measuringthe physical properties of saliva (viscosity test, spinnability test),and (5) questionnaire methods. Whether saliva secretion in a subject isreduced or not can be evaluated by using any one of these methods, or acombination of two or more of these methods.

(B-I) Additive for Composition for Intraoral Use or Oral Intake

The additive for compositions for intraoral use or oral intake(hereinafter also simply referred to “the additive of the presentinvention” is characterized by containing enzymatically modifiedisoquercitrin and a thickening polysaccharide.

(B-I-1) Enzymatically Modified Isoquercitrin

The enzymatically modified isoquercitrin used in the present inventionis as explained above in (A-I-1), the disclosure of which is hereinincorporated by reference in its entirety.

(B-I-2) Thickening Polysaccharide

The thickening polysaccharide used in the present invention is an ediblethickening polysaccharide approved for use in foods and beverages orpharmaceutical products for oral administration. The thickeningpolysaccharide is as explained above in (A-I-2), whose disclosure isherein incorporated by reference in its entirety.

The proportion of the thickening polysaccharide contained in theadditive of the present invention may vary according to the form of theadditive. For example, when the additive is in the form of a powder,granules, or tablets, the proportion of the thickening polysaccharidecan be usually suitably selected from the range of 1 mass % or more andless than 100 mass %, preferably in the range of 3 to 90 mass %, andmore preferably 5 to 80 mass %. When the additive is in the form of apaste or liquid, the proportion of the thickening polysaccharide can beusually suitably selected from the range of 0.1 to 10 mass %, preferably0.2 to 8 mass %, and more preferably 0.3 to 6 mass %.

The proportion of the thickening polysaccharide to the enzymaticallymodified isoquercitrin in the additive of the present invention can beusually selected from the range of 0.2 to 500 parts by mass, per part bymass of the enzymatically modified isoquercitrin (in terms of rutin; thesame applies hereinafter). The proportion of the thickeningpolysaccharide to the enzymatically modified isoquercitrin in theadditive of the present invention can be selected and adjusted accordingto the form of the oral composition prepared by addition. For example,when the additive of the present invention is an additive for preparinga sol composition for oral intake, the proportion of the thickeningpolysaccharide may be in the range of 0.2 to 400 parts by mass,preferably 0.3 to 350 parts by mass, and more preferably 0.4 to 300parts by mass, per part by mass of the enzymatically modifiedisoquercitrin. When the additive of the present invention is an additivefor preparing a gel composition for oral administration, the proportionof the thickening polysaccharide is in the range of 1 to 500 parts bymass, preferably 2 to 450 parts by mass, and more preferably 2.5 to 350parts by mass, per part by mass of the enzymatically modifiedisoquercitrin. When the additive of the present invention is an additivefor preparing a food or beverage prepared by processing cereal grains (aprocessed grain food or beverage), the proportion of the thickeningpolysaccharide may be, for example, 0.01 to 3000 parts by mass,preferably 0.05 to 2000 parts by mass, and more preferably 0.1 to 1200parts by mass, per part by mass of the enzymatically modifiedisoquercitrin.

(B-I-3) Other Components

As long as the effect of the present invention is not impaired, theadditive of the present invention may contain any edible components inaddition to the above components.

Examples of edible components include, but are not limited to, thosementioned above in (A-I-3), the disclosure of which, including thedisclosure regarding the proportion of edible metal salts, is hereinincorporated by reference in its entirety.

(B-I-4) Form, Preparation Method, Effect, Use, Etc., of the Additive

The form of the additive of the present invention is not limited, aslong as the additive comprises at least the enzymatically modifiedisoquercitrin and thickening polysaccharide. For example, a solid form,a paste form, and a liquid form can be used. Preferably, the form of theadditive is a solid form, such as a powder, granules, or tablets; or aliquid form. The additive is more preferably in the form of granulesbecause of its excellent solubility in water.

The additive of the present invention can be prepared according to theform in a usual manner. For example, the additive in the form of apowder can be prepared by powder-mixing enzymatically modifiedisoquercitrin and a thickening polysaccharide with an excipient.Alternatively, the additive in the form of a powder can also be preparedby drying (e.g., spray-drying, freeze-drying) a liquid containingenzymatically modified isoquercitrin and a thickening polysaccharide.The additive in the form of granules can be prepared by granulating thepowder mixture. Alternatively, the additive in the form of granules canalso be prepared by spraying enzymatically modified isoquercitrin as abinder solution over a powder-thickening polysaccharide. The additive inthe form of tablets can be prepared by forming the powdery or granularadditive into tablets using a tableting machine. The liquid additive canbe prepared by adding enzymatically modified isoquercitrin and athickening polysaccharide to a solvent (preferably water).

When water or the composition for intraoral use or oral intakecontaining water (e.g., a liquid composition for intraoral use or oralintake) is ingested or administered, the additive of the presentinvention is usually used by being added to the target composition forintraoral use or oral intake. The target composition for intraoral useor oral intake is water itself, or formulated in such a manner that thecomposition contains at least a predetermined amount of water.Therefore, when the additive of the present invention is added and mixedby stirring, the viscosity increases so that the composition becomes asol or gel.

The temperature of the target composition for intraoral use or oralintake when the additive of the present invention is added and mixed maybe, for example, a temperature at which the additive of the presentinvention is dissolved or dispersed, and a thickening polysaccharidecontained in the additive is thereby hydrated and swells. Thistemperature may vary depending on the type of thickening polysaccharide,and can be suitably set in the range of 1 to 100° C.

The amount of the additive of the present invention added to the targetcomposition for intraoral use or oral intake can be suitably adjustedaccording to the kind, water content, purpose, and use of the targetcomposition for intraoral use or oral intake. For example, the additiveis preferably added in a proportion such that the enzymatically modifiedisoquercitrin content of the composition for intraoral use or oralintake after incorporating the additive of the present invention thereinis 0.0005 to 1 mass %. The enzymatically modified isoquercitrin contentof the composition for intraoral use or oral intake is preferably 0.001to 0.7 mass %, and more preferably 0.0015 to 0.5 mass %.

When the target composition for intraoral use or oral intake is a foodor beverage prepared by processing cereal grains (a processed grain foodor beverage), the additive is particularly preferably added in aproportion such that the enzymatically modified isoquercitrin content ofthe composition for oral intake after incorporating the additive of thepresent invention therein is 0.003 to 0.5 mass %. The enzymaticallymodified isoquercitrin content of the processed grain food or beverageis preferably 0.005 to 0.45 mass %, and more preferably 0.0065 to 0.4mass %.

The additive of the present invention can be used for imparting a salivasecretion-promoting effect to the target composition for intraoral useor oral intake. In other words, the additive of the present invention isused to prepare a composition for intraoral use or oral intake having asalivation-promoting effect. In this sense, the additive of the presentinvention can be called a salivator. The “salivator” has the action ofincreasing the amount of saliva secretion. In the present invention, asstated above, the “salivator” imparts the effect of increasing theamount of saliva secretion (salivation-promoting action) to thecomposition for intraoral use or oral intake.

The additive of the present invention can be used to impart aneasy-to-swallow property to the target composition for intraoral use ororal intake. In other words, the additive of the present invention isused to prepare a composition for intraoral use or oral intake that canbe easily swallowed. In this sense, the additive of the presentinvention can be called a swallowing-assisting agent (or adeglutition-improving agent). Further, the additive of the presentinvention can be used to impart an easy-to-chew property to thecomposition for intraoral use or oral intake. In other words, theadditive of the present invention is used for preparing a compositionfor intraoral use or oral intake that can be easily chewed. In thissense, the additive of the present invention can be called achewing-assisting agent (or a mastication-improving agent).

The concepts or definitions of “swallowing” and “chewing” are asexplained above in (A-I-5), the disclosure of which is hereinincorporated by reference herein in its entirety.

(B-I-5) Composition for Intraoral Use or Oral Ingestion to which theAdditive of the Present Invention is Added

The composition for intraoral use to which the additive of the presentinvention is added is foods or beverages, or pharmaceutical products forintraoral use, which are ingested or taken (administered) from the mouthor remain in the mouth. Examples include foods and beverages, such asgums, gummi candies, films, and tablets (e.g., lozenges); andpharmaceutical products for intraoral use, such as mouthwashes,toothpastes, films, tablets (e.g., lozenges). The target composition fororal intake to which the additive of the present invention is added isfoods or beverages, or pharmaceutical products for oral administration,which are ingested or taken (administered) from the mouth. Thecomposition for intraoral use and the composition for oral intake aredifferent in that the composition for intraoral use refers tocompositions used in the state of residing in the mouth for a certainperiod of time (including compositions that are swallowed, andcompositions that are not swallowed), whereas the composition for oralintake is usually swallowed without residing in the mouth except for thetime necessary for chewing. However, the composition for intraoral useand the composition for oral intake are not necessarily strictlydistinguished from each other, and may partially overlap. To make adistinction from the composition for oral intake according to thepresent invention described later, the compositions for intraoral use ororal intake to which the additive of the present invention is to beadded may also be referred to as the “target compositions for intraoraluse or oral intake,” and the foods or beverages or pharmaceuticalproducts for intraoral use or oral intake to which the additive of thepresent invention is to be added may also be referred to as the “targetfoods or beverages” and “target pharmaceutical products for intraoraluse or oral intake.”

Specific examples of the target foods or beverages include beveragessuch as water (including mineral water), soft drinks (e.g., tea-basedbeverages, fruit beverages, vegetable beverages, coffee beverages, cocoabeverages, sports supplement drinks, carbonated drinks, lacticbeverages, soy milks, soy milk beverages, isotonic drinks, etc.), milkproducts (e.g., cow's milk, lactic acid bacteria beverages, etc.); soupproducts such as soup, miso soup, shiruko (sweet red bean soup with ricecake), and amazake (sweet drink made from fermented rice); confectioneryproducts (including paste or gel confectionery, liquefied confectioneryproducts (e.g., minced foods, paste foods, and weaning foods));nutritional supplement beverages and foods (including nutritionalsupplement beverages or foods in paste or gel form, liquid nutritionalsupplement beverages and foods (e.g., minced foods, paste foods, andweaning foods)); staple foods (including, for example, cooked ricefoods, noodles, baked goods, etc., liquid staple foods (e.g., mincedfoods, paste foods, and weaning foods)); side dishes (includingliquefied side dishes (e.g., minced foods, paste foods, and weaningfoods)); concentrated liquid foods; enteral nutrients (orallyadministered or orally ingested); and the like. The aboveconfectioneries, nutritional supplement foods and beverages, staplefoods, side dishes, etc., include processed grain foods and beveragesobtained by processing cereal grains. The minced foods herein refer tofoods obtained by fragmenting food materials by a cutter, a mixer, orthe like. The paste foods refer to foods obtained by forming foodmaterials into a paste. There is no strict distinction between mincedfoods and paste foods. Both are adjusted to have high fluidity to allowpersons with difficulty in swallowing or chewing etc. to easily enjoyeating. The fluidity of minced foods and paste foods can be adjusted byadding water, if necessary.

Examples of the processed grain foods include foods and beveragesobtained by processing cereal grains, such as grain (barley, wheat),Japanese barnyard millet, foxtail millet, rice, buckwheat, beans (e.g.,soybean), and corns. Examples include, but are not limited to,confectioneries (for example, baked confectioneries such as cookies,biscuits, crackers, doughnuts, rusks, cakes (including pancakes),madeleines, macaroons, pies, and cream puffs), fried confectionaries,and steamed confectioneries); cooked rice products; noodles (e.g., udon(noodles made from wheat flour), buckwheat noodles, ramen noodles,harusame (starch noodle), macaroni, and wonton); baked goods (includingChinese steamed buns and pizzas); wrapped foods (e.g., jiaozi (aChinese-style dumpling with minced pork and vegetable stuffing), shaomai(a steamed meat dumpling), wonton, and spring roll) and wrappersthereof; premix powders for producing flour-containing foods, such aspancake mix, mix for takoyaki (grilled dumplings with bits of octopus),mix for okonomiyaki (grilled spicy pancakes with a wide variety ofingredients), crepe mix, batter mix) (for example, pancake mix, takoyakimix, okonomiyaki mix, crepe mix, and batter mix), cornflakes, and thelike. Many of these processed grain foods or beverages have a low watercontent, tend to be dry, and have difficulty in forming an alimentarybolus; and become sticky when water is added, thus poorly melting in themouth or becoming difficult to swallow. In particular, many cooked ricefoods, and confectioneries, noodles, and baked goods mainly comprisingflour have physical properties that make them difficult for persons withreduced chewing function or reduced swallowing function to swallow. Whenthe additive of the present invention is applied to gain processed foodsand beverages having such physical properties, melt-in-the-mouthproperties of the processed grain products can be enhanced. Further,when such foods are eaten, a feeling of cohesiveness in the mouth can beobtained and/or a feeling of adhesion to the pharynx can be reduced.Therefore, processed grain foods and beverages that are easy to swallowcan be prepared.

The target pharmaceutical products for intraoral use or oral intake isnot particularly limited, as long as it is used in the mouth or orallyadministered. Examples include powders (powdered medicine), granules,tablets (including lozenges and chewable agents), pills, capsules,films, and liquids (health drinks).

When the additive of the present invention is incorporated into thetarget composition for intraoral use or oral intake, the composition forintraoral use or oral intake preferably contains at least apredetermined amount of water. The water content of the targetcomposition for intraoral use or oral intake is preferably 60 mass % ormore, preferably 70 mass % or more, and more preferably 80 mass % ormore. Accordingly, when the water content of the target composition forintraoral use or oral intake (foods and beverages, pharmaceuticalproducts for intraoral use or oral administration) is less than 60 mass%, the water content of the composition for intraoral use or oral intakeis preferably adjusted to the range described above before the additiveof the present invention is added. For example, when the targetcomposition for intraoral use or oral intake is a pharmaceuticalpreparation in the form of a powder or granules, a method comprisingadding water to achieve a water content of 60 mass, or more anddispersing such a preparation in water can be used.

(B-II) Composition for Intraoral Use or Oral Ingestion and ProductionMethod Therefor

The present invention provides a composition for intraoral use or oralintake comprising enzymatically modified isoquercitrin and a thickeningpolysaccharide. The composition for intraoral use or oral intakeincludes a composition for intraoral use or oral intake comprising theadditive of the present invention described above. The composition forintraoral use of the present invention is a food or beverage or apharmaceutical product for intraoral use that is ingested or taken(administered) from the mouth and is retained in the mouth. Examplesinclude foods and beverages, such as gums, films, and tablets; andpharmaceutical products for intraoral use, such as mouthwashes,toothpastes, films, and tablets. The composition for oral administrationof the present invention is not limited as long as it can be orallyingested or administered. Examples of the composition include foods andbeverages and pharmaceutical products for oral administration.

The composition for intraoral use or oral intake of the presentinvention can be prepared by using enzymatically modified isoquercitrinand a thickening polysaccharide, preferably using the additive of thepresent invention described above.

The proportion of enzymatically modified isoquercitrin in thecomposition for intraoral use or oral intake of the present invention isnot particularly limited as long as the effect of the present inventionis provided. The proportion may be usually, for example, in the range of0.0005 to 1 mass %, preferably 0.001 to 0.7 mass %, more preferably0.0015 to 0.5 mass %. When the target composition for intraoral use ororal intake is a food or beverage prepared by processing cereal grains(a processed grain food or beverage), the proportion of theenzymatically modified isoquercitrin in the oral composition of thepresent invention is particularly preferably 0.003 to 0.5 mass %, morepreferably 0.005 to 0.45 mass %, and even more preferably 0.0065 to 0.4mass %.

The proportion of the thickening polysaccharide in the composition forintraoral use or oral intake of the present invention may be, forexample, in the range of 0.2 to 500 parts by mass per part by mass ofthe enzymatically modified isoquercitrin contained in the compositionfor intraoral use or oral intake of the present invention. Theproportion of the thickening polysaccharide to the enzymaticallymodified isoquercitrin contained in the composition for intraoral use ororal intake of the present invention can be selected and adjustedaccording to the type of composition for intraoral use or oral intake towhich the thickening polysaccharide is added. For example, when thecomposition for intraoral use or oral intake of the present invention isa sol composition for intraoral use or oral intake, the proportion ofthe thickening polysaccharide may be, for example, 0.2 to 400 parts bymass, preferably 0.3 to 350 parts by mass, and more preferably 0.4 to300 parts by mass, per part by mass of the enzymatically modifiedisoquercitrin contained in the composition for intraoral use or oralintake. When the composition for intraoral use or oral intake of thepresent invention is a gel composition for intraoral use or oral intake,the proportion of the thickening polysaccharide may be, for example, 1to 500 parts by mass, preferably 2 to 450 parts by mass, and morepreferably 2.5 to 350 parts by mass, per part by mass of theenzymatically modified isoquercitrin contained in the composition forintraoral use or oral intake. When the composition for intraoral use ororal intake of the present invention is a processed grain food orbeverage, the proportion of the thickening polysaccharide may be, forexample, 0.01 to 3000 parts by mass, preferably 0.05 to 2000 parts bymass, and more preferably 0.1 to 12000 parts by mass, per part by massof the enzymatically modified isoquercitrin.

As long as the above conditions are met, there is no particularlimitation. The proportion of the thickening polysaccharide may beusually, for example, in the range of 0.01 to 10 mass %, preferably 0.02to 8 mass %, and more preferably 0.03 to 6 mass %, per 100 mass % of thecomposition for intraoral use or oral intake of the present invention.

The composition for intraoral use or oral intake of the presentinvention can be prepared by adding enzymatically modified isoquercitrinand a thickening polysaccharide to the target composition for intraoraluse or oral intake of the present invention before, preferablyimmediately before, ingesting or taking (administering) the composition.The composition for intraoral use or oral intake of the presentinvention can be prepared by adding enzymatically modified isoquercitrinand a thickening polysaccharide to a target composition for intraoraluse or oral intake and mixing by stirring. After mixing by stirring, ifnecessary, the resulting product is allowed to stand or cooled tosolidify the product into a gel, thus preparing the composition forintraoral use or oral intake of the present invention. As theenzymatically modified isoquercitrin and thickening polysaccharide, theadditive of the present invention described above can be convenientlyused.

The target composition for intraoral use or oral intake include, forexample, those disclosed above in (B-I-5). The disclosure is hereinincorporated by reference. When the water content of the targetcomposition for intraoral use or oral intake is less than 60 mass %, thewater content of the target composition for intraoral use or oral intakeis preferably adjusted to 60 mass % or more by, for example, addingwater.

The temperature conditions for adding enzymatically modifiedisoquercitrin and a thickening polysaccharide (or the additive of thepresent invention) to the composition for intraoral use or oral intake,or the temperature conditions for mixing by stirring may be anytemperature at which the enzymatically modified isoquercitrin andthickening polysaccharide can be dissolved or dispersed in the targetcomposition for intraoral use or oral intake.

Among thickening polysaccharides, deacylated gellan gum, carrageenan,pectin, alginates, etc., have the property of increasing viscosity orgelling in the presence of a soluble metal salt. Therefore, when such athickening polysaccharide is used, a soluble metal salt is preferablyused together. The soluble metal salt to be used is not limited, andpreferable examples include sodium salts (e.g., sodium chloride, sodiumcitrate, etc.), potassium salts (e.g., potassium chloride, potassiumcitrate, etc.), calcium salts (e.g., calcium chloride, calcium citrate,etc.), magnesium salts (e.g., magnesium chloride etc.), and the like.When an edible metal salt is used, a preferable proportion of the ediblemetal salt in the composition for intraoral use or oral intake of thepresent invention is usually 0.00001 to 15 mass, and preferably 0.00002to 10 mass %.

The manner of mixing by stirring is not particularly limited. Forexample, mixing may be performed by stirring with a chopstick, a spoon,or a fork; or by stirring using a stirring tool, such as a householdmixer, a food processor, a rotary beater, a blender, a cooking cutter,or a propeller stirrer.

The composition for intraoral use or oral intake of the presentinvention thus obtained can be prepared in the form of a gel or a solhaving the predetermined physical properties.

The “gel” referred to herein specifically means that when the product isallowed to stand at a product temperature of 20° C. for 1 to 2 minutes,its shape is retained and the product does not flow under its ownweight; i.e., its shape does not change between the state 1 minute afterbeing allowed to stand at a product temperature of 20° C., and the state2 minutes after being allowed to stand at 20° C. The “sol” means thatwhen allowed to stand at a product temperature of 20° C., the productflows under its own weight, and its shape is not retained; or its shapechanges between the state 1 minute after being allowed to stand at aproduct temperature of 20° C., and the state 2 minutes after beingallowed to stand at 20° C. These all refer to the state under standardatmospheric pressure (1 atm) conditions.

When the composition for intraoral use or oral intake of the presentinvention is in the form of a gel, the composition for intraoral use ororal intake preferably has a fracture strain of 0.3 to 0.8, morepreferably 0.4 to 0.8, and still more preferably 0.45 to 0.75, asdetermined at a product temperature of 20° C. under standard atmosphericpressure conditions.

The “fracture strain” referred to herein can be determined by thefollowing measurement method.

Method for Determining the Fracture Strain

(a) As a test sample, a composition for intraoral use or oral intake (atest sample)(product temperature: 20° C.) having a cylindrical shapewith a diameter of 20 mm and a height of 10 mm is prepared.

(b) Using a texture analyzer (TA-XT-2i (produced by Stable MicroSystems) texture analyzer), the test sample is compressed. Thecompression is performed at a rate of 10 mm/s using a jig having adiameter of 100 mm.

(c) The fracture point is determined from a “stress-strain curve”obtained by the compression, and the fracture strain is calculated bythe following formula.

Fracture strain=A/B  [Math. 2]

A: Distance (mm) from the position where the jig first comes intocontact with the test sample (the upper surface of the test sample) tothe point where the sample is broken by being contacted and compressedwith the jig (fracture point).B: Height of the test sample (=10 mm)

When the fracture strain of the gel composition for intraoral use ororal intake has a fracture strain of 0.3 to 0.8, preferably 0.4 to 0.8,and more preferably 0.45 to 0.75, the oral composition fragmented bychewing in the mouth is appropriately gathered into a mass (provides afeeling of cohesiveness), thus forming an alimentary bolus that can beeasily chewed and swallowed even by persons with reduced chewingfunction or reduced swallowing function. If the fracture strain exceeds0.8, time is required to fragment the oral composition in the mouth, anddifficulty in swallowing may occur.

The gel composition for intraoral use or oral intake comprising bothenzymatically modified isoquercitrin and a thickening polysaccharidetends to have a higher saliva secretion-promoting effect as the gelcomposition for intraoral use or oral intake has a smaller fracturestrain. Specifically, when the gel food or beverage (20° C.) has afracture strain of 0.3 to 0.8, preferably 0.4 to 0.8, and morepreferably 0.45 to 0.75, a particularly remarkable salivation-promotingeffect is provided.

When the composition for intraoral use or oral intake of the presentinvention is in the form of a gel, the composition for intraoral use ororal intake preferably has a “hardness” of 500,000 N/m² or less,preferably 500 to 400,000 N/m², and more preferably 500 to 250,000 N/m²,as measured at a product temperature of 20° C. under standardatmospheric pressure conditions. The “hardness” can be determinedaccording to the Universal Design Food Voluntary Standard, secondedition (the Japan Care Food Conference). More specifically, thehardness can be determined by the following measurement method.

Method for Measuring the Hardness

A test sample is placed in a container having a diameter of 40 mm and aheight of 20 mm. Using a texture analyzer (TA-XT-2i (produced by StableMicro Systems) texture analyzer) and a resin plunger having a diameterof 20 mm and a height of 8 mm, compression measurement is performedtwice at a compression speed of 10 mm/sec with a clearance of 5 mm. Themaximum stress at the time of the first compression is defined as“hardness” (N/m²).

In particular, when the “hardness” is in the range of 500 to 500,000N/m², preferably 500 to 250,000 N/m², the obtained oral composition iseasy to chew or swallow, even for persons with reduced chewing function.

When the composition for intraoral use or oral intake of the presentinvention is in the form of a sol, the composition for intraoral use ororal intake preferably has a viscosity of 0.006 Pa·s or more, morepreferably 0.006 to 0.6 Pa·s, and still more preferably 0.008 to 0.4Pa·s, at a shear rate of 100 s⁻¹. The “viscosity” referred to herein canbe measured by using a jig (made of resin) with corn-and-plate geometryhaving a diameter of 50 mm, and reading the viscosity value at ameasurement temperature of the sample (product temperature) of 20° C.and at a shear rate of 100 s⁻¹. ARES-LS1 (produced by TA Instruments)can be used as the measuring apparatus.

The composition for intraoral use or oral intake thus obtained, whichcontains a thickening polysaccharide in addition to enzymaticallymodified isoquercitrin, has an excellent salivation-promoting function,as compared with oral compositions not containing a thickeningpolysaccharide, as shown in the Experimental Examples described below.Therefore, the composition for intraoral use or oral intake can beprovided as a food or beverage or a pharmaceutical product for intraoraluse or oral administration suitable for persons with reduced salivasecretion function. The composition for intraoral use or oral intake ofthe present invention, which contains a thickening polysaccharide inaddition to enzymatically modified isoquercitrin, has an excellenteasy-to-swallow property and easy-to-chew property, as compared withcompositions for intraoral use or oral intake not containing athickening polysaccharide. Therefore, the composition for intraoral useor oral intake of the present invention can be provided as a food orbeverage that can be suitably ingested by persons with reduced chewingfunction and/or persons with reduced swallowing function, or as apharmaceutical product for intraoral use or oral administration that canbe suitably taken by persons with reduced chewing function and/orpersons with reduced swallowing function.

When the composition for intraoral use or oral intake of the presentinvention is a processed grain food or beverage, the timing of addingthe composition is not particularly limited as long as the compositioncontains enzymatically modified isoquercitrin and a thickeningpolysaccharide before ingestion or administration (taking). For example,when the composition for intraoral use or oral intake of the presentinvention is a baked confectionery product, such as cookies,enzymatically modified isoquercitrin and a thickening polysaccharide canbe added to a dough before baking to provide a processed grain food orbeverage with improved melt-in-the-mouth sensation.

EXAMPLES

The following Experimental Examples and Formulation Examples areprovided to better clarify the constitution and effects of the presentinvention. However, the present invention is by no means affected bythese Experimental Examples etc.

Experimental Example 1 (1) Preparation of Test Samples

An enzymatically modified isoquercitrin preparation (SAN EMIQ® No. 1:produced by San-Ei Gen F.F.I.) (containing enzymatically modifiedisoquercitrin in a proportion of 10 mass % in terms of α-glucosylisoquercitrin (as rutin), and further containing dextrin as anothercomponent); α-glucosylrutin (αG rutin) (produced by Toyo Sugar RefiningCo., Ltd.); and quercetin (produced by LKT Laboratories, Inc.) were usedas test substances. These test substances were individually dissolved inion exchange water to prepare aqueous solutions of the test substancesat the various concentrations shown in Table 1 (test samples).

Table 1 shows the contents of the enzymatically modified isoquercitrinpreparation and αG rutin in terms of rutin (molarity) and the molarconcentration of quercetin, in addition to the test substance content ofeach test sample (mass %).

TABLE 1 Content (molarity) Enzymatically modified αG rutin in terms ofisoquercitrin preparation (content rutin or molarity (α-glucosylisoquercitrin in terms of quercetin content (in terms of rutin)) ofrutin) Quercetin (μM) (mass %) (mass %) (mass %) 25 μM 0.0153 (0.00153)— — 75 μM 0.0458 (0.00458) 0.0116 0.0023 150 μM  0.0915 (0.00915) 0.02320.0045 750 μM  0.4575 (0.04575) 0.1161 0.0227 3750 μM  2.2875 (0.22875)0.5805 0.1133

The molarity of quercetin and the content of rutin contained in theenzymatically modified isoquercitrin and αG rutin (both are quercetinglycosides) were calculated by the following method.

Quantification of Quercetin (Molarity)

The quantity of quercetin (molarity) was calculated with the molecularweight of quercetin being defined as 302.

Amount (Molarity) of Enzymatically Modified Isoquercitrin and αG Rutinin Terms of Rutin

The quantity of enzymatically modified isoquercitrin and αG rutin(molarity) was determined according to the quantification methoddescribed on the “Enzymatically Modified Isoquercitrin” page in theSpecifications and Standards for Food Additives, 8th Edition (TheMinistry of Health, Labour and Welfare, Japan). The details are asdescribed above.

For example, when the α-glucosyl isoquercitrin content of theenzymatically modified isoquercitrin preparation (sample A) (in terms ofrutin ((C₂₇H₃₀O₁₆)) calculated by the above formula [Math. 1] is 10 mass%, 6100 g of the enzymatically modified isoquercitrin preparation(sample A) (610×(100/10)=6100) (610 is the molecular weight of rutin)corresponds to 1 mol of enzymatically modified isoquercitrin.Accordingly, in the above case, for example, to achieve a molarity ofenzymatically modified isoquercitrin in an aqueous solution of 75 μM(75×10⁻⁶ mol/L), 0.4575 g (6100 g/mol×75×10⁻⁶ mol) of the enzymaticallymodified isoquercitrin preparation (sample A) must be dissolved (ordispersed) in 1 L of water.

(2) Evaluation of Salivation-Promoting Effect

Using 3 healthy persons (males, average age: 31.3 years old) aspanelists, the salivation-promoting effect of the test samples preparedabove was evaluated. Persons whose circadian variation of salivasecretion is relatively similar were selected as the panelists fromcandidates.

The evaluation was performed using 15 g of each test sample per testaccording to the following method. As a blank, a test was performed inthe same manner using 15 g of water in place of the test samples.

(i) After 15 g of each sample is placed in the mouth and retained for 5seconds, the sample is swallowed at one time.(ii) After 5 seconds, absorbent cotton (37.5 mm×37.5 mm×4 mm) is placedunder (the back of) the tongue, and retained for 2 minutes.(iii) The absorbent cotton is removed from under the tongue, and theweight (g) of the cotton is measured. This weight is compared with theweight of the absorbent cotton before being placed in the mouth tocalculate the difference in weight.

The above test was performed using the same test sample twice perpanelist, and the average was calculated. Based on the average of eachpanelist, the average and standard deviation of all of the panelistswere calculated.

(3) Evaluation Results

Table 2 and FIG. 1 show the evaluation results (the average of 3panelists). The results are shown as numerical values (relative values)standardized by setting the saliva secretion amount obtained by usingthe blank (water) as 1.

TABLE 2 Amount of salivation (standardized Standard Test sample withwater) deviation 25 μM enzymatically modified 1.209 0.443 isoquercitrinaqueous solution 75 μM enzymatically modified 1.794 0.522 isoquercitrinaqueous solution 75 μM αG rutin aqueous solution 0.910 0.356 75 μMquercetin aqueous solution 0.989 0.388 150 μM enzymatically modified1.907 0.117 isoquercitrin aqueous solution 150 μM αG rutin aqueoussolution 0.841 0.093 150 μM quercetin aqueous solution 0.826 0.133 750μM enzymatically modified 2.259 0.162 isoquercitrin aqueous solution 750μM αG rutin aqueous solution 0.872 0.232 750 μM quercetin aqueoussolution 1.032 0.139 3750 μM enzymatically modified 2.034 0.170isoquercitrin aqueous solution 3750 μM αG rutin aqueous solution 0.9320.123 3750 μM quercetin aqueous solution 1.132 0.276

As is clear from this result, the enzymatically modified isoquercitrinin a concentration range of 25 to 750 μM exhibits a salivation-promoting(increasing) effect in a molarity-dependent manner. In particular, theeffect is provided immediately after placing the enzymatically modifiedisoquercitrin in the mouth, or after swallowing the enzymaticallymodified isoquercitrin. This effect was not observed in quercetin itselfor αG rutin, which is also a quercetin glycoside, like enzymaticallymodified isoquercitrin; this effect is specific to enzymaticallymodified isoquercitrin.

The above results clearly show that oral intake of samples containingenzymatically modified isoquercitrin (intraoral use, oral intake) cansignificantly increase saliva secretion.

Experimental Example 2

Xanthan gum was added as a thickening polysaccharide to the test samplesof Experimental Example 1 (aqueous solutions of enzymatically modifiedisoquercitrin, αG rutin, and quercetin) to thicken the samples. Theresulting compositions were evaluated for salivation-promoting effect inthe same manner as in Experimental Example 1 to investigate whethercontaining or not containing xanthan gum (being thickened or not beingthickened) makes a difference in the effect.

(1) Preparation of Test Samples

Test substances (enzymatically modified isoquercitrin preparation, αGrutin, and quercetin) were dissolved in drinking water, and adjusted sothat the rutin content (molarity) of the structure of each compound was150 μM (see Table 1). Further, xanthan gum was added to the aqueoussolutions, so that the content thereof was 0.1 mass %, thus thickeningthe solutions. For comparison, xanthan gum-free aqueous solutions (anaqueous enzymatically modified isoquercitrin solution, an aqueous αGrutin solution, an aqueous quercetin solution) at a concentration of 150μM in terms of rutin were prepared in the same manner as in ExperimentalExample 1.

The viscosity of each sample was measured using a fluid rheometer(ARES-LS1, produced by TA Instrument) under the following measurementconditions.

Measurement Conditions

Measurement temperature: 20° C.Geometry: corn-and-plate with a diameter of 50 mm and a gap of 0.05 mmShear rate: 100 s⁻¹.

(2) Evaluation of Salivation-Promoting Effect and Results Thereof

The salivation-promoting effect of each test sample prepared above wasevaluated in the same manner as in Experimental Example 1 (the panelistswere also the same). Table 3 and FIG. 2 show the evaluation results (theaverage of 3 panelists).

All of the thickened samples had a viscosity of 20 mPa·s, and all of thenon-thickened samples had a viscosity of 1 mPa·s (20° C.).

TABLE 3 α-Glucosyl Amount of isoquercitrin salivation content (content(standardized Standard in terms of rutin) with water) deviationThickened Enzymatically 150 μM 2.511 0.904 modified isoquercitrin αGrutin 150 μM 0.719 0.167 Quercetin 150 μM 0.868 0.109 Non- Enzymatically150 μM 1.907 0.117 thickened modified isoquercitrin αG rutin 150 μM0.841 0.093 Quercetin 150 μM 0.826 0.133

As is clear from these results, thickened enzymatically modifiedisoquercitrin by incorporating a thickening polysaccharide increases thesalivation-promoting effect (salivation-increasing effect) of theenzymatically modified isoquercitrin. On the other hand, thisenhancement effect on the salivation-promoting effect(salivation-increasing effect) by incorporating a thickeningpolysaccharide was not observed in quercetin itself or αG rutin, whichis also a quercetin glycoside like enzymatically modified isoquercitrin;and this effect was thus found to be specific to enzymatically modifiedisoquercitrin.

The above results of Experimental Examples 1 to 2 show that when acomposition for intraoral use or a composition for oral intake thatcomprises enzymatically modified isoquercitrin and that is thickened byfurther incorporating a thickening polysaccharide or the like isingested as a salivator from the mouth, the amount of saliva secretionis further significantly increased. The results also show that theadditive for a composition for intraoral use or the additive for acomposition for oral intake according to the present invention issuitable as an additive for preparing a thickened composition forintraoral use or oral intake, or as a swallowing-assisting agent.

Experimental Example 3 (1) Preparation of Test Samples

Various materials in the amounts shown in the formulations of Table 4were powder-mixed and compression-molded (tableted) at a tabletingpressure of 5 kN using a desktop tableting machine (produced byIchihashi Seiki Co., Ltd.) to prepare enzymatically modifiedisoquercitrin-containing tablets weighing 1.5 g per tablet (tablet size:18 mmϕ).

(2) Evaluation of Salivation-Promoting Effect and Results Thereof

The salivation-promoting effect of each test sample prepared above wasevaluated in the same manner as in Experimental Example 1 (the panelistswere also the same).

TABLE 4 (mass %) Comparative Example Example Sorbitol 97.1 97High-sweetness sweetener preparation* 0.15 0.15 Powdery flavor 0.75 0.75Enzymatically modified isoquercitrin — 0.1 preparation** (α-glucosylisoquercitrin (0.01) content (in terms of rutin)) Sucrose fatty acidester 2 2 Total 100 100 *High-sweetness sweetener preparation: “SanSweet ® SA-8020” (containing 24 mass % sucralose, 18 mass % acesulfamepotassium, and 58 mass % reduced palatinose), produced by San-Ei GenF.F.I., Inc. **Enzymatically modified isoquercitrin preparation: “SanEmiq ® No. 1” (containing 10 mass % α-glucosyl isoquercitrin (in termsof rutin), and further containing dextrin as another component),produced by San-Ei Gen F.F.I. Inc.

(3) Evaluation Results

The average of 3 panelists was shown as numerical values standardized bysetting the amount of saliva secretion obtained by using the blank(water) as 1, and the amounts of saliva secretion were evaluated. Thevalue obtained by subtracting the amount of saliva secretion(standardized with water) obtained in the Comparative Example from theamount of saliva secretion (standardized with water) obtained in theExample was 1.52. The administration or intake of tablets containingenzymatically modified isoquercitrin significantly increases the amountof saliva secretion, as compared with the administration or intake oftablets not containing enzymatically modified isoquercitrin.

Example 4: Salivation-Promoting Effect of Sol Compositions for IntraoralUse or Oral Intake (No. 1) (1) Preparation of Test Samples

The additives for compositions for intraoral use or oral intakecontaining enzymatically modified isoquercitrin and a thickeningpolysaccharide in the proportions shown in Table 1 were dissolved inwater (20° C.) to prepare sol compositions for intraoral use or oralintake (Test samples 4-1 to 4-5). The viscosity (shear rate: 100 s⁻¹)was measured at a product temperature of 20° C. under standardatmospheric pressure conditions. As a control, enzymatically modifiedisoquercitrin was dissolved in water (20° C.) in the proportion shown inTable 5 to prepare a composition for intraoral use or oral intake(Control sample 4). The viscosity (shear rate: 100 s⁻¹) was measured ata product temperature of 20° C. under standard atmospheric pressureconditions. Xanthan gum (produced by San-Ei Gen F.F.I., Inc.) was usedas the thickening polysaccharide. “SAN EMIQ® No. 1,” which is anenzymatically modified isoquercitrin preparation produced by San-Ei GenF.F.I., Inc., was used as the enzymatically modified isoquercitrin. Theenzymatically modified isoquercitrin tablet contains enzymaticallymodified isoquercitrin in a proportion of 10 mass % in terms ofα-glucosyl isoquercitrin (as rutin [C₂₇H₃₀O₁₆]), and further containsdextrin as another component.

The viscosity of the control sample and test samples at a shear rate of100 s⁻¹ was measured using an ARES-LS1 fluid rheometer (jig: 50 mm indiameter, with cone-and-plate geometry, made of resin, 0.05 mm in gap)(produced by TA Instruments) at a sample temperature of 20° C. understandard atmospheric pressure conditions.

TABLE 5 (mass %) Control Test sample sample 4 4-1 4-2 4-3 4-4 4-5Enzymatically 0.0915 0.0915 0.0915 0.0915 0.0915 0.0915 modified(0.00915) (0.00915) (0.00915) (0.00915) (0.00915) (0.00915)isoquercitrin preparation* (α-glucosyl isoquercitrin (content in termsof rutin (mass %)**) Xanthan gum — 0.04 0.10 0.50 1.00 2.80 (XG) WaterBalance Balance Balance Balance Balance Balance Total 100 100 100 100100 100 Proportion of 0 4.4 10.9 54.6 109.3 306 XG per part by mass ofα- glucosyl isoquercitrin (content in terms of rutin) (parts by mass)Shear 1.23 9.05 19.12 61.96 95.76 364.82 viscosity at a shear rate of100 s⁻¹ (mPa · s) *Enzymatically modified isoquercitrin preparation:“San Emiq ® No. 1,” produced by San-Ei Gen F.F.I., Inc. **Proportion(mass %) of α-glucosyl isoquercitrin (in terms of rutin) in the sample(100 mass %)

The content of enzymatically modified isoquercitrin contained in Controlsample 4 and Test samples 4-1 to 4-5 was 150 μM as the α-glucosylisoquercitrin content in terms of rutin. The content of enzymaticallymodified isoquercitrin in terms of rutin can be determined according tothe quantification method described on the “Enzymatically ModifiedIsoquercitrin” page in the Specifications and Standards for FoodAdditives, 8th Edition (The Ministry of Health, Labour and Welfare,Japan) as described above. For example, when the α-glucosylisoquercitrin content (as rutin (C₂₇H₃₀O₁₆)) of an enzymaticallymodified isoquercitrin preparation (sample A) is 10 mass %, 6100 g(610×(100/10)=6100) of the enzymatically modified isoquercitrinpreparation (sample A) (610 is the molecular weight of rutin) correspondto 1 mol of the enzymatically modified isoquercitrin. Accordingly, inthe above case, to achieve a molarity of the enzymatically modifiedisoquercitrin in an aqueous solution of 150 μM (150×10⁻⁶ mol/L), 0.915 g(6100 g/mol×150×10⁻⁶ mol) of the enzymatically modified isoquercitrinpreparation (sample A) must be dissolved (or dispersed) in 1 L of water.

(2) Measurement of Salivation-Promoting Effect

Using 3 healthy subjects with no salivation abnormalities (subjects A toC: average age: 31.3 years old) as panels, the salivation-promotingeffects of the compositions for intraoral use or oral intake (Controlsample 4 and Test samples 4-1 to 4-5) and 20° C. water (blank) wereevaluated by the method described below.

(a) 15 g of each sample (blank (water), Control sample 4, or Testsamples 4-1 to 4-5) is placed in the mouth and retained for 5 seconds,and then swallowed at one time.(b) After swallowing and after a lapse of 5 seconds, absorbent cottonwith a size of 3.75 cm×3.75 cm is placed under the tongue, and retainedfor 2 minutes. The weight of the absorbent cotton is measured inadvance.(c) After 2 minutes, the absorbent cotton is recovered, and the weightis measured.(d) From the weight change of the absorbent cotton before and afterbeing placed under the tongue, the amount of saliva secretion by intakeof each sample (blank (water), Control sample 4, or Test samples 4-1 to4-5) was calculated.

Table 6 and FIG. 3 show the results. To eliminate the individualdifference in the amount of saliva secretion, Table 6 and FIG. 3 shownumerical values (relative values) standardized by setting the averageof saliva secretion amount in each subject determined by using water(blank) as 1.

TABLE 6 Proportion of XG per part Shear by mass of α-glucosyl viscosityisoquercitrin (in terms of rutin) at a shear Average (parts by mass)(α-glucosyl rate of of saliva isoquercitrin (as rutin):XG = 1:x) 100 s⁻¹secretion (mass ratio) (mPa · s) amount* Water — 1.00 (blank) Control —1.91 sample 4 Test sample 1:4.4  9.05 2.59 4-1 Test sample 1:10.9 19.122.48 4-2 Test sample 1:54.6 61.96 3.46 4-3 Test sample  1:109.3 95.763.66 4-4 Test sample 1:306  364.82 2.50 4-5 *The average of salivasecretion amount is a relative value with the saliva secretion amount(the average) obtained by intake of the blank (water) being set as 1.

As shown in Table 6, when the compositions for intraoral use or oralintake (Test Samples 4-1 to 4-5) containing an additive for compositionsfor intraoral use or oral intake, which contained both enzymaticallymodified isoquercitrin and a thickening polysaccharide (xanthan gum wasused in this experiment), are ingested, the amount of saliva secretionincreased in all of the subjects, as compared with intake of the blank(water). These compositions for intraoral use or oral intake had notaste or odor. It is thus expected that when the additives for oralcompositions (Examples 4-1 to 4-5) used to prepare the above Testsamples 4-1 to 4-5 are used, salivation-promoting effects can beimparted to compositions for intraoral use or oral intake, withoutadversely affecting the flavor of the compositions for intraoral use ororal intake to which the additives are applied.

Control sample 4 not containing a thickening polysaccharide increasedthe amount of saliva secretion as compared with water (blank). However,the increase in the saliva secretion amount achieved by Control sample 4was small as compared with that achieved by Test samples 4-1 to 4-5, andControl sample 4 exhibited a lower salivation-promoting effect.

The above results show that a thickening polysaccharide (xanthan gum)itself, when used alone, does not have a salivation-promoting effect;however, when the thickening polysaccharide is used with enzymaticallymodified isoquercitrin, the salivation-promoting effect of theenzymatically modified isoquercitrin is enhanced.

Example 5: Evaluation of Salivation-Promoting Effect of Sol Compositionsfor Intraoral Use or Oral Intake (No. 2) (1) Preparation of Test Samples

Additives for compositions for intraoral use or oral intake containingenzymatically modified isoquercitrin and a thickening polysaccharide inthe proportions shown in Table 7 were dissolved in water (20° C.) toprepare sol compositions for intraoral use or oral intake (Test Samples5-1 to 5-5). Xanthan gum (produced by San-Ei Gen F.F.I., Inc.) was usedas the thickening polysaccharide. “San Emiq® No. 1,” which is anenzymatically modified isoquercitrin preparation produced by San-Ei GenF.F.I., Inc., was used as the enzymatically modified isoquercitrin.

TABLE 7 (mass %) Test sample 5-1 5-2 5-3 5-4 5-5 Enzymatically 0.01530.0458 0.0915 0.4575 2.2875 modified (0.00153) (0.00458) (0.00915)(0.04575) (0.22875) isoquercitrin preparation* (α-glucosyl isoquercitrincontent (in terms of rutin): mass %**) α-Glucosyl 25 μM 75 μM 150 μM 750μM 3750 μM isoquercitrin content (in terms of rutin)* (molarity) Xanthangum (XG) 0.10 0.10 0.10 0.10 0.10 Water Balance Balance Balance BalanceBalance Total 100 100 100 100 100 Proportion of XG per- 65.4 21.8 10.92.2 0.4 part by mass of α-glucosyl isoquercitrin (in terms of rutin)(parts by mass) *Enzymatically modified isoquercitrin preparation: “SanEmiq ® No. 1,” produced by San-Ei Gen F.F.I., Inc. **Proportion (mass %)of α-glucosyl isoquercitrin (in terms of rutin) in the test sample (100mass %)

(2) Measurement of Salivation-Promoting Effect

Using 3 healthy subjects with no salivation abnormalities (subjects A toC: average age: 31.3 years old) as panelists, the salivation-promotingeffect of compositions for intraoral use or oral intake (Test samples5-1 to 5-5) and water (blank) (all 20° C.) were evaluated in the samemanner as in Experimental Example 4.

Table 8 and FIG. 4 show the results. To eliminate the individualdifference in the amount of saliva secretion, Table 8 and FIG. 4 shownumerical values (relative values) standardized by setting the averageof the saliva secretion amount in each subject determined by using water(blank) as 1.

TABLE 8 Molar concentration α-Glucosyl of α-glucosyl isoquercitrinAverage of isoquercitrin (in terms of saliva content rutin):XG = 1:xsecretion (in terms of rutin) (mass ratio) amount* Water (blank) — —1.00 Test sample 5-1 25 μM 1:65.4 1.52 Test sample 5-2 75 μM 1:21.8 1.98Test sample 5-3 150 μM 1:10.9 2.48 Test sample 5-4 750 μM 1:2.2  2.62Test sample 5-5 3750 μM 1:0.4  2.48 *The average of saliva secretionamount is a relative value with the saliva secretion amount (theaverage) obtained by intake of the blank (water) being set as 1.

As shown in Table 8, intake of the compositions for intraoral use ororal intake (Test Samples 5-1 to 5-5), which contained an additive forcompositions for intraoral use or oral intake containing bothenzymatically modified isoquercitrin and a thickening polysaccharide(xanthan gum), increased the amount of saliva secretion in all of thesubjects, as compared with intake of the blank (water); and asalivation-promoting effect was observed. These compositions forintraoral use or oral intake had no taste or odor. Incorporating Testsamples 5-1 to 5-5 (additives for compositions for oral intake) intocompositions for intraoral use or oral intake is thus expected to impartsalivation-promoting effects to the compositions for intraoral use ororal intake.

The above results show that when a thickening polysaccharide (xanthangum) is used with enzymatically modified isoquercitrin, thesalivation-promoting effect of the enzymatically modified isoquercitrinincreases in a manner dependent on the content of enzymatically modifiedisoquercitrin used.

Example 6: Salivation-Promoting Effect of Gel Compositions for IntraoralUse or Oral Intake (No. 1)

The additives for compositions for intraoral use or oral intakecontaining enzymatically modified isoquercitrin and a thickeningpolysaccharide in the proportions shown in Table 9 were dissolved inwater (20° C.) to prepare gel compositions for intraoral use or oralintake, and their salivation-promoting effects were evaluated.

(1) Preparation of Control Samples and Test Samples

The gel compositions for intraoral use or oral intake were preparedfollowing the procedures described below.

1. Among the components shown in Table 9, components (1) to (4) aremixed.2. The obtained powder mixture is added to ion-exchange water (6),heated to 90° C., and dissolved while stirring at 1300 rpm for 10minutes.3. Component (5) is added to the aqueous solution of components (1) to(4), and the weight is corrected with ion-exchange water (6), ifnecessary.4. The aqueous solution of (1) to (6) is placed in a resin containerhaving a multilayer structure including an oxygen barrier layer (LamiconCup, produced by Toyo Seikan Co., Ltd.), and the container is sealed.5. The solution is sterilized (85° C., for 30 minutes).6. The container is cooled to 8° C. to gel the solution, thus obtaininga gel composition for intraoral use or oral intake.7. The composition is preserved in a 5° C. refrigerator.

TABLE 9 (mass %) Control Sample Test Sample 6-1 6-2 6-3 6-4 6-5 6-1 6-26-3 6-4 6-5 (1) Granulated sugar 10 10 10 10 10 10 10 10 10 10 (2)Deacylated gellan gum 0.03 0.25 3 0.48 0.25 0.03 0.25 3 0.48 0.25 (3)Highly acylated gellan — — — 0.12 0.25 — — — 0.12 0.25 gum (4)Enzymatically modified — — — — — 0.0915 0.0915 0.0915 0.0915 0.0915isoquercitrin preparation* (α- (—) (—) (—) (—) (—) (0.00915) (0.00915)(0.00915) (0.00915) (0.00915) glucoside isoquercitrin (in terms ofrutin) (mass %)**) (5) Calcium lactate 0.1 0.25 0.1 0.1 0.1 0.1 0.25 0.10.1 0.1 (6) Water Balance Balance Balance Balance Balance BalanceBalance Balance Balance Balance Total 100 100 100 100 100 100 100 100100 100 *Enzymatically modified isoquercitrin preparation: “San Emiq ®No. 1” (containing 10 mass % of enzymatically modified isoquercitrin (interms of rutin), and further containing dextrin as another component),produced by San-Ei Gen F.F.I., Inc. **Proportion of α-glucosylisoquercitrin (in terms of rutin) in the test sample (100 mass %) (mass%) Test samples 6-1 to 6-5 contain enzymatically modified isoquercitrinas α-glucosyl isoquercitrin in a molarity (in terms of rutin) of 150 μM.

(2) Measurement of Fracture Strain and Hardness of Control Samples andTest Samples (Compositions for Intraoral Use or Oral Intake) (2-1)Measurement of Fracture Strain

The aqueous solutions of components (1) to (6) of control samples andtest samples shown in Table 9 were poured into glass tubular containers(inner diameter: 20 mm, height: 10 mm, thickness: 1.5 mm), and cooled inan 8° C. water tank for 2 hours to solidify the solutions. Thecontainers were then allowed to stand at 5° C. for 15 hours to preparegel compositions for intraoral use or oral intake having a cylindricalshape (diameter: 20 mm, height: 10 mm) (Control samples 6-1 to 6-5 andTest samples 6-1 to 6-5).

The fracture strain of the gel compositions for intraoral use or oralintake having a cylindrical shape (diameter: 20 mm, height: 10 mm)prepared above were measured following the procedures described belowusing a texture analyzer (TA-XT-2i (produced by Stable Micro Systems)texture analyzer, probe: P/50 (ϕ 50 mm)). For the measurement, thecontrol samples or test samples were adjusted to a product temperatureof 20° C.

(a) Using a jig with a diameter of 100 mm, the control samples or testsamples were compressed at a rate of 10 mm/s (start position: 20 mm,clearance: 1 mm).(b) The yield point of the “load-strain curve” obtained by compression(point at which stress rise is mitigated: peak or inflection point) isdefined as the fracture point. The fracture point of the control samplesand test samples was determined according to the following formula.

Fracture strain=A/B  [Math. 3]

A: Distance (mm) from the point where the jig first comes into contactwith the test sample (the upper surface of the test sample) to the pointwhere the sample is broken by being compressed with the jig (point offracture).B: Height of the test sample (=10 mm)

Table 10 shows the results. The values shown in the table are theaverage of the values measured 3 times by using each of the controlsamples and test samples.

TABLE 10 (mass %) Control Sample Test Sample 6-1 6-2 6-3 6-4 6-5 6-1 6-26-3 6-4 6-5 Fracture strain 0.341 0.408 0.491 0.585 0.736 0.327 0.3930.490 0.589 0.727

(2-2) Measurement of Hardness

Aqueous solutions of the control samples and test samples (1) to (6)shown in Table 9 were poured into stainless steel containers having acylindrical shape (inner diameter: 40 mm, height: 15 mm), and cooled inan 8° C. water tank for 2 hours to solidify the solutions. Thecontainers were then allowed to stand at 5° C. for 15 hours to obtaingel compositions for intraoral use or oral intake contained in thecontainer having a diameter of 40 mm and a height of 15 mm (controlsamples 6-1 to 6-5 and test samples 6-1 to 6-5).

The hardness (N/m²) of the gel compositions for intraoral use or oralintake having a cylindrical shape (inner diameter: 40 mm, height: 15 mm)was measured using a texture analyzer (TA-XT-2i (produced by StableMicro Systems) texture analyzer, probe: P/20 (ϕ20 mm)). Specifically,using a resin plunger with a diameter of 20 mm and a height of 8 mm,compression measurement was performed twice at a compression rate of 10mm/s and with a clearance of 5 mm. The maximum stress in the firstcompression is defined as “hardness” (N/m²). For the measurement, thecontrol samples and test samples were adjusted to a product temperatureof 20° C.

Table 11 shows the results.

TABLE 11 (mass %) Control Sample Test Sample 6-1 6-2 6-3 6-4 6-5 6-1 6-26-3 6-4 6-5 Hardness 634 40,129 388,694 28,074 22,413 712 36,937 377,50329,045 22,215 (N/m²)

(3) Evaluation of Salivation-Promoting Effect of Control Samples andTest Samples (Compositions for Intraoral Use or Oral Intake)

Using 3 healthy subjects with no salivation abnormalities (subjects A toC; average age: 31.3 years old) as panelists, salivation-promotingeffects of the compositions for intraoral use or oral intake (Controlsamples 6-1 to 6-5, Test samples 6-1 to 6-5, product temperature: 20°C.) and 20° C. water (blank) were evaluated by the method describedbelow.

(a) 10 g of each sample (Control samples 6-1 to 6-5, Test samples 6-1 to6-5) is placed in the mouth and freely chewed for 20 seconds, and thenswallowed at one time. 10 g of water is placed in the mouth and retainedin the mouth for 20 seconds, and then swallowed at one time.(b) After swallowing and after a lapse of 5 seconds, absorbent cottonwith a size of 3.75 cm×3.75 cm×4 mm is placed under the tongue, andretained for 2 minutes. The weight of the absorbent cotton is measuredin advance.(c) After 2 minutes, the absorbent cotton is recovered, and the weightis measured.(d) From the weight change of the absorbent cotton before and afterbeing placed under the tongue, the amount of saliva secretion by intakeof each sample (blank (water), Control samples 6-1 to 6-5, Test samples6-1 to 6-5) was calculated.

Table 12 and FIG. 5 show the results. Table 12 shows the amount ofsaliva secretion as well as the fracture strain and hardness. Toeliminate the individual difference in the amount of saliva secretion,Table 12 and FIG. 5 show numerical values (relative values) standardizedby setting the average of the saliva secretion amount in each subjectdetermined by using water (blank) as 1.

TABLE 12 Average of saliva Fracture Hardness secretion strain (N/m²)amount* Control Sample 6-1 (not containing 0.341 634 1.30 enzymaticallymodified isoquercitrin preparation) Control Sample 6-2 (not containing0.408 40,129 1.63 enzymatically modified isoquercitrin preparation)Control Sample 6-3 (not containing 0.491 388,694 1.65 enzymaticallymodified isoquercitrin preparation) Control Sample 6-4 (not containing0.585 28,074 1.28 enzymatically modified isoquercitrin preparation)Control Sample 6-5 (not containing 0.736 22,413 1.46 enzymaticallymodified isoquercitrin preparation) Test Sample 6-1 0.327 712 3.61(containing 150 μM enzymatically modified isoquercitrin preparation)Test Sample 6-2 0.393 36,937 2.42 (containing 150 μM enzymaticallymodified isoquercitrin preparation) Test Sample 6-3 0.490 377,503 3.52(containing 150 μM enzymatically modified isoquercitrin preparation)Test Sample 6-4 0.589 29,045 2.99 (containing 150 μM enzymaticallymodified isoquercitrin preparation) Test Sample 6-5 0.727 22,215 2.99(containing 150 μM enzymatically modified isoquercitrin preparation)*The average of saliva secretion amount is a relative value with thesaliva secretion amount (the average) by intake of the blank (water)being set as 1.

As shown in the above table, a clear difference in the amount of salivasecretion was observed between the gel compositions for intraoral use ororal intake containing enzymatically modified isoquercitrin (testsamples 6-1 to 6-5), and the gel compositions for intraoral use or oralintake not containing enzymatically modified isoquercitrin (controlsamples 6-1 to 6-5). The results also confirmed that the amount ofsaliva secretion is significantly promoted and increased by chewing thegel compositions for intraoral use or oral intake containingenzymatically modified isoquercitrin in the oral cavity, or swallowingthe compositions.

Experimental Example 7: Salivation-Promoting Effect of Gel Compositionsfor Intraoral Use or Oral Intake (No. 2)

The additive for a composition for intraoral use or oral intakecontaining enzymatically modified isoquercitrin and a thickeningpolysaccharide in a proportion shown in Table 13 was dissolved in water(20° C.) to prepare a gel composition for intraoral use or oral intake.The salivation-promoting effect of the gel composition for intraoral useor oral intake was evaluated following the method disclosed inExperimental Example 6.

(1) Preparation of Control Sample and Test Samples

Gel compositions for intraoral use or oral intake were preparedfollowing the procedures described below.

1. Among the components shown in Table 13, components (1) to (3) arepowder-mixed.2. The powder mixture is added to ion-exchange water (5), heated to 90°C., and dissolved while stirring at 1300 rpm for 10 minutes.3. Component (4) is added to the aqueous solution and the weight iscorrected with ion-exchange water (5), if necessary.4. The aqueous solution of components (1) to (5) prepared above isplaced in a resin container having a multilayer structure including anoxygen barrier layer (Lamicon Cup, produced by Toyo Seikan Co., Ltd.),and the container is sealed.5. The solution is sterilized (85° C., for 30 minutes).6. The container is cooled to 8° C. to gel the solution, thus producinga gel composition for intraoral use or oral intake.7. The composition is preserved in a 5° C. refrigerator.

The composition for intraoral use or oral intake thus prepared had afracture strain of 0.511 to 0.526, and a hardness of 41,528 to 54,170N/m².

TABLE 13 Control Test sample sample 7 7-1 7-2 7-3 7-4 7-5 7-6 (1)Granulated 10  10 10 10 10 10 10 sugar (2) Deacylated   0.55 0.55 0.550.55 0.55 0.55 0.55 gellan gum (3) Enzymatically 0 0.00612 0.0153 0.04580.0915 0.4575 2.2875 modified (0) (0.000612) (0.00153) (0.00458)(0.00915) (0.04575) (0.22875) isoquercitrin preparation* (as α-glucosideisoquercitrin (in terms of rutin) (mass %)*) (Concentration (0 μM) (10μM) (25 μM) (75 μM) (150 μM) (750 μM) (3750 μM) of α-glucosideisoquercitrin in terms of rutin) (4) Calcium   0.1 0.1 0.1 0.1 0.1 0.10.1 lactate (5) Water Balance Balance Balance Balance Balance BalanceBalance Total 100  100 100 100 100 100 100 *Enzymatically modifiedisoquercitrin preparation: “San Emiq ® No. 1” (containing 10 mass % ofenzymatically modified isoquercitrin (in terms of rutin) and furthercontaining dextrin as another component), produced by San-Ei Gen F.F.I.,Inc. *Proportion of α-glucosyl isoquercitrin (in terms of rutin) in thetest sample (100 mass %) (mass %)

(2) Evaluation of Salivation-Promoting Effect of Test Samples(Compositions for Intraoral Use or Oral Intake)

Using 3 healthy subjects with no salivation abnormalities (subjects A toC: average age: 31.3 years old) as panelists, the salivation-promotingeffects of the compositions for intraoral use or oral intake (Controlsample 7, Test samples 7-1 to 7-6, product temperature: 20° C.) and 20°C. water (blank) were evaluated by the method described below.

(a) After 10 g of each sample (Control sample 7 and Test samples 7-1 to7-6) is placed in the mouth and freely chewed for 20 seconds, the sampleis swallowed at one time. After 10 g of water is placed in the mouth andretained in the mouth for 20 seconds, the water is swallowed at onetime.(b) After swallowing and after a lapse of 5 seconds, absorbent cottonwith a size of 3.75 cm×3.75 cm×4 mm is placed under the tongue andretained for 2 minutes. The weight of the absorbent cotton is measuredin advance.(c) After 2 minutes, the absorbent cotton is collected and the weight ismeasured.(d) From the weight change of the absorbent cotton before and afterbeing placed under the tongue, the amount of saliva secretion by intakeof each sample (blank (water), Control sample 7, Test samples 7-1 to7-6) was calculated.

Table 14 and FIG. 6 show the results. To eliminate the individualdifference in the amount of saliva secretion, Table 14 and FIG. 6 shownumerical values (relative values) standardized by setting the averageof the saliva secretion amount in each subject determined by using water(blank) as 1.

TABLE 14 Average of saliva Sample (concentration of α-glucosyl FractureHardness secretion isoquercitrin, in terms of rutin) strain (N/m²)amount* Control sample 7 (0 μM) 0.526 41528 1.70 Test sample 7-1 (10 μM)0.523 50679 1.83 Test sample 7-2 (25 μM) 0.511 42880 2.61 Test sample7-3 (75 μM) 0.517 46429 2.92 Test sample 7-4 (150 μM) 0.521 54170 3.37Test sample 7-5 (750 μM) 0.513 49575 3.78 Test sample 7-6 (3750 μM)0.518 49914 3.18 *The average of saliva secretion amount is a relativevalue with the saliva secretion amount (the average) obtained by intakeof a blank sample (water) being set as 1.

As shown in Table 14, although Control sample 7 in the form of a gel notcontaining enzymatically modified isoquercitrin also increased theamount of saliva secretion, a combination of enzymatically modifiedisoquercitrin with a thickening polysaccharide (Test samples 7-1 to 7-6)was confirmed to increase the amount of saliva secretion moresignificantly than the control sample. The results further confirmedthat the effect of increasing the amount of saliva secretion isdependent on the amount of enzymatically modified isoquercitrinincorporated (dose-dependent).

The above results of Experimental Examples 6 to 7 show that when gelcompositions for intraoral use or oral intake that comprise a salivatorcomprising a thickening polysaccharide in addition to enzymaticallymodified isoquercitrin and that have a fracture strain within the rangeof 0.3 to 0.8 or/and a hardness of 500 to 500,000 N/m² are orallyingested, saliva secretion significantly increases. The results furthershow that the additive for compositions for intraoral use or oral intakeaccording to the present invention is suitable as an additive forpreparing a gel composition for intraoral use or oral intake having aspecific fracture strain or/and hardness as described above.

1. An additive for a composition for intraoral use or oral intakecomprising enzymatically modified isoquercitrin and a polysaccharide forthickening.
 2. The additive for a composition for intraoral use or oralintake according to claim 1, wherein the polysaccharide for thickeningis at least one member selected from the group consisting of xanthangum, locust bean gum, guar gum, tara gum, deacylated gellan gum, nativegellan gum, pectin, alginic acid salts, gelatin, agar, psyllium seedgum, and carrageenan.
 3. The additive for a composition for intraoraluse or oral intake according to claim 1, which comprises thepolysaccharide for thickening in a proportion of 0.2 to 500 parts bymass per part by mass of the enzymatically modified isoquercitrin. 4.The additive for a composition for intraoral use or oral intakeaccording to claim 1, wherein the composition for intraoral use or oralintake is a food or beverage, or a pharmaceutical product.
 5. Theadditive for a composition for intraoral use or oral intake according toclaim 1, wherein the composition for intraoral use or oral intake is afood or beverage or a pharmaceutical product that is ingested by oradministered to at least one person selected from the group consistingof persons with reduced salivation function, persons with reducedswallowing function, and persons with reduced chewing function.
 6. Theadditive for a composition for intraoral use or oral intake according toclaim 1, which is an additive for preparing a composition for intraoraluse or oral intake in the form of a gel having at least one of thefollowing physical properties (1) and (2), or in the form of a solhaving the following physical property (3): (1) breaking strain: 0.3 to0.8; (2) hardness: 500 to 500,000 N/m²; and (3) viscosity (shear rate:100[S⁻¹]): 0.006 to 0.6 Pa·s.
 7. A composition for intraoral use or oralintake, comprising the additive for a composition for intraoral use ororal intake according to claim
 1. 8. The composition for intraoral useor oral intake according to claim 7, which is a food or beverage or apharmaceutical product that is ingested by or administered to at leastone person selected from the group consisting of persons with reducedsalivation function, persons with reduced swallowing function, andpersons with reduced chewing function.
 9. The composition for intraoraluse or oral intake according to claim 7, which is a food or beverage ora pharmaceutical product in the form of a gel having at least one of thefollowing physical properties (1) and (2), or in the form of a solhaving the following physical property (3): (1) breaking strain: 0.3 to0.8; (2) hardness: 500 to 500,000 N/m²; and (3) viscosity (shear rate:100[S⁻¹]): 0.006 to 0.6 Pa·s.
 10. A method for preparing a compositionfor intraoral use or oral intake, comprising the additive for acomposition for intraoral use or oral intake according to claim 1, saidmethod comprising the step of incorporating enzymatically modifiedisoquercitrin and a polysaccharide for thickening, or the additive for acomposition for intraoral use or oral intake according to claim 1 into afood or beverage or a pharmaceutical product having a water content of60 mass % or more.
 11. A salivator comprising enzymatically modifiedisoquercitrin as an active ingredient, or enzymatically modifiedisoquercitrin and a polysaccharide for thickening as active ingredients.12. The salivator according to claim 11, which is in the form of acomposition for intraoral use or oral intake.
 13. The salivatoraccording to claim 11, which is in the form of a syrup, health drink,liquid, emulsion, oil, spray, gel, paste, tablet, chewable agent,lozenge, pill, granule, powder, dry syrup, film, or stick-shapedpreparation.
 14. (canceled)
 15. (canceled)
 16. A composition forintraoral use or oral intake, comprising the additive for a compositionfor intraoral use or oral intake according to claim
 6. 17. Thecomposition for intraoral use or oral intake according to claim 16,which is a food or beverage or a pharmaceutical product that is ingestedby or administered to at least one person selected from the groupconsisting of persons with reduced salivation function, persons withreduced swallowing function, and persons with reduced chewing function.18. The composition for intraoral use or oral intake according to claim17, which is a food or beverage or a pharmaceutical product in the formof a gel having at least one of the following physical properties (1)and (2), or in the form of a sol having the following physical property(3): (1) breaking strain: 0.3 to 0.8; (2) hardness: 500 to 500,000 N/m²;and (3) viscosity (shear rate: 100[S⁻¹]): 0.006 to 0.6 Pa·s.
 19. Amethod for preparing a composition for intraoral use or oral intake,comprising the additive for a composition for intraoral use or oralintake according to claim 6, said method comprising the step ofincorporating enzymatically modified isoquercitrin and a polysaccharidefor thickening, or the additive for a composition for intraoral use ororal intake according to claim 6 into a food or beverage or apharmaceutical product having a water content of 60 mass % or more.